Substituted bicyclic heterocyclic compounds as prmt5 inhibitors

ABSTRACT

The invention relates to substituted bicyclic heterocyclic compounds of formula (I), pharmaceutically acceptable salts thereof and pharmaceutical compositions for treating diseases, disorders or conditions associated with the overexpression of PRMT5 enzyme. The invention also relates to methods of treating diseases, disorders or conditions associated with the overexpression of PRMT5 enzyme.

FIELD OF THE INVENTION

The invention relates to substituted bicyclic heterocyclic compounds offormula (I), pharmaceutically acceptable salts thereof andpharmaceutical compositions for treating diseases, disorders orconditions associated with the overexpression of PRMT5 enzyme. Theinvention also relates to methods of treating diseases, disorders orconditions associated with the overexpression of PRMT5 enzyme.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of Indian Provisional PatentApplications Nos. IN 201721044886 filed on Dec. 13, 2017, IN201821040029 filed on Oct. 23, 2018, and IN 201821024634 filed on Jul.2, 2018, the disclosures of which are incorporated herein by referencein their entirety for all purposes.

BACKGROUND TO THE INVENTION

Methylation of proteins is a common post-translational modification thataffects the protein's activity and its interaction with other biologicalmolecules. N-methylation typically occurs on the nitrogen atoms ofarginine, lysine and histidine residues and there are different familiesof enzymes that catalyze the methylation reaction, each being specificto the amino acid residue that will be methylated.

A family of 9 enzymes, called Protein Arginine N-Methyl Transferases(PRMTs), are responsible for the methylation of the guanidinium group ofarginine. The guanidinium group of arginine bears 2 terminal nitrogenatoms that undergo monomethylation or dimethylation. Depending on thetype of dimethylation, the enzymes are further classified as type I ortype II. Type I PRMTs catalyse the monomethylation or the asymmetricdimethylation whereas type II enzymes catalyse the symmetricdimethylation. Some of the substrates that undergo methylation arehistones, Sm ribonucleoproteins, MRE11 and p53 binding protein 1.

The methylation of arginine side-chains has an important role to play invarious cell functions that include transcription activation as well astranscription repression, mRNA translation, pre-mRNA splicing, proteintrafficking and signal transduction. It also occurs on myriadsubstrates. The enzymatic activity of the PRMTs hence affects cellularprocesses like cell proliferation, repair of damaged DNA as well as cellcycle and cell death. It has been shown that PRMT enzyme-mediatedhypermethylation leads to certain disease conditions like cancer (NatureReviews Cancer 2013, 13, p 37; Cellular and Molecular Life Sciences2015, 72, p 2041; Trends in Biochemical Sciences 2011, 36, p 633).

At present, the most studied type II enzyme is PRMT5, which is conservedacross the eukaryotic organisms. Overexpression of PRMT5 is linked withcarcinogenesis and decreased patient survival in several humanmalignancies (Cell Mol Life Sci., 2015, 72, p 2041). PRMT5 directlyinteracts with proteins often dysregulated or mutated in cancers, hencea putative oncogene (Mol Cell Biol, 2008, 28, p 6262). PRMT5 mediatedtranscriptional repression of tumor suppressor genes like p53, RB-1,ST7, or upregulation of Cyclin D1, CDK4, CDK6, eLF4E, MITF, FGFR3associate with the oncogenesis in both solid tumors and hemaologicalmalignancies. PRMT5 is located in the nucleus as well as the cytoplasmand its overexpression has been linked to a wide range of cancersincluding, but not limited to, glioblastoma multiforme (Oncogene, 2017,36, p 263), prostate cancer (Oncogene, 2017, 36, p 1223), and pancreaticcancer (Science, 2016, 351, p 1214), mantle cell lymphoma (NatureChemical Biology, 2015, 11, p 432), non-Hodgkin's lymphomas and diffuselarge B-cell lymphoma (Journal of Biological Chemistry, 2013, 288, p35534), acute myeloid leukemia (Leukemia, 2018, 32, p 499), acutelymphoblastic leukemia (AACR; Cancer Research 2017; 77(13Suppl):Abstract nr 1128), multiple myeloma (Leukemia, 2018, 32, p 996),non-small cell lung cancer (The Biochemical Journal, 2012, 446, p 235),small cell lung cancer (AACR; Cancer Research 2017; 77(13Suppl):Abstract nr DDT02-04), breast cancer (Cell Reports, 2017, 21, p3498), triple negative breast cancer (AACR; Cancer Res 2015; 75(15Suppl):Abstract nr 4786), gastric cancer (International Journal ofOncology, 2016, 49, p 1195), colorectal cancer (Oncotarget, 2015, 6, p22799), ovarian cancer (J Histochem Cytochem 2013, 61, p 206), bladdercancer (Clinical Cancer Research, 2018, CCR-18-1270), hepatocellularcancer (Oncology Reports, 2018, 40, p 536), melanoma (PLoS One, 2013, 8,e74710; J Clin Invest. 2018, 128, p⁵17), sarcoma (Oncology Letters,2018, 16, p 2161), oropharyngeal squamous cell carcinoma (Oncotarget,2017, 8, p 14847), chronic myelogenous leukemia (J Clin Invest, 2016,126, p³⁹⁶1), epidermal squamous cell carcinoma (Carcinogenesis, 2017,38, p 827), nasopharyngeal carcinoma (Oncology Reports, 2016, 35, p1703), neuroblastoma (Molecular Oncology, 2015, 9, p 617), endometrialcarcinoma (Gynecol Oncol., 2016, 140, p 145), cervical cancer(Pharmazie, 2018, 73, p 269). These findings have led to furtherresearch which show that inhibiting PRMT5 reduces cell proliferation(Molecular and Cellular Biology 2008, 28, p 6262, The Journal ofBiological Chemistry 2013, 288, p 35534).

Inhibitors of arginine methyl transferases were first disclosed in 2004by Cheng et al in the Journal of Biological Chemistry—Vol. 279 (23), p.23892. Since then, various other compounds and substances having greaterselectivity towards either type I or type II arginine methyltransferases have been disclosed. Other publications that disclose smallmolecules as inhibitors in relation to PRMT5 are: WO2011077133,WO2011079236, WO2014100695, WO2014100716, WO2014100719, WO2014100730,WO2014100734, WO2014128465, WO2014145214, WO2015200677, WO2015200680,WO2015198229, WO2016022605, WO2016034671, WO2016034673, WO2016034675,WO2016038550, WO2016135582, WO2016145150, WO2016178870, WO2017032840 andACS Medicinal Chemistry Letters 2015, 6, p 408.

SUMMARY OF THE INVENTION

In accordance with one aspect, the invention provides compound ofgeneral formula (I), a stereoisomer thereof, or a pharmaceuticallyacceptable salt thereof,

wherein,L₁ is selected from —CR^(a)R^(b)—, —NR^(a)—, S, and O;

Z═CH or N;

R^(a) and R^(b) are independently selected at each occurrence fromhydrogen, substituted or unsubstituted alkyl, and substituted orunsubstituted cycloalkyl;ring A is selected from,

R^(c) and R^(d) are selected from substituted or unsubstituted alkyl ortogether with the carbon atoms to which they are attached form a C₃-C₆cycloalkyl ring;R is selected from —NR⁴R⁵, hydrogen, halogen, substituted orunsubstituted alkyl, substituted or unsubstituted alkoxy, substituted orunsubstituted heteroaryl and substituted or unsubstituted cycloalkyl;R¹ and R² together with the carbon atoms to which they are attached forma bond in order to form a —C═C—; or R¹ and R² together with the carbonatoms to which they are attached form a cyclopropane ring;R^(2′) and R^(2a) which may be same or different and are independentlyselected from hydrogen and substituted or unsubstituted alkyl;R³ is independently selected at each occurrence from halogen, cyano,nitro, substituted or unsubstituted alkyl, —OR⁶, —NR⁷R⁸, substituted orunsubstituted cycloalkyl, —C(O)OH, —C(O)O-alkyl, —C(O)R⁹, —C(O)NR⁷R⁸,—NR⁷C(O)R⁹, substituted or unsubstituted aryl, substituted orunsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl;R⁴ and R⁵ are independently selected from hydrogen, substituted orunsubstituted alkyl, and substituted or unsubstituted cycloalkyl;R⁶ is selected from hydrogen, substituted or unsubstituted alkyl, andsubstituted or unsubstituted cycloalkyl;R⁷ and R⁸ are independently selected from hydrogen, substituted orunsubstituted alkyl, and substituted or unsubstituted cycloalkyl;R⁹ is selected from substituted or unsubstituted alkyl and substitutedor unsubstituted cycloalkyl;R¹⁰ is selected from hydrogen, halogen, and substituted or unsubstitutedalkyl;‘n’ is an integer ranging from 0 to 4, both inclusive;when an alkyl group is substituted, it is substituted with 1 to 4substituents independently selected from oxo (═O), halogen, cyano,cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR^(7a), —C(═O)OH,—C(═O)O(alkyl), —NR^(8a)R^(8b), —NR^(8a)C(═O)R^(9a), and—C(═O)NR^(8a)R^(8b); when the heteroaryl group is substituted, it issubstituted with 1 to 4 substituents independently selected fromhalogen, nitro, cyano, alkyl, haloalkyl, perhaloalkyl, cycloalkyl,heterocyclyl, aryl, heteroaryl, —OR^(7a), —NR^(8a)R^(8b),—NR^(7a)C(═O)R^(9a), —C(═O)R^(9a), —C(═O)NR^(8a)R^(8b), —S₂-alkyl,—C(═O)OH, and —C(═O)O-alkyl; when the heterocycle group is substituted,it is substituted either on a ring carbon atom or on a ring hetero atom,and when it is substituted on a ring carbon atom, it is substituted with1 to 4 substituents independently selected from oxo (═O), halogen,cyano, alkyl, cycloalkyl, perhaloalkyl, —OR^(7a), —C(═O)NR^(8a)R^(8b),—C(═O)OH, —C(═O)O-alkyl, —N(H)C(═O)(alkyl), —N(H)R^(a), and —N(alkyl)₂;and when the heterocycle group is substituted on a ring nitrogen, it issubstituted with substituents independently selected from alkyl,cycloalkyl, aryl, heteroaryl, —SO₂(alkyl), —C(═O)R^(9a), and—C(═O)O(alkyl); when the heterocycle group is substituted on a ringsulfur, it is substituted with 1 or 2 oxo (═O) group(s);R^(7a) is selected from hydrogen, alkyl, perhaloalkyl, and cycloalkyl;R^(8a) and R^(8b) are each independently selected from hydrogen, alkyl,and cycloalkyl; andR^(9a) is selected from alkyl and cycloalkyl.The details of one or more embodiments of the invention set forth inbelow are only illustrative in nature and not intended to limit to thescope of the invention. Other features, objects and advantages of theinventions will be apparent from the description and claims.According to one embodiment, the invention provides compounds having thestructure of Formula (II), a stereoisomer thereof, or a pharmaceuticallyacceptable salt thereof,

-   -   wherein,    -   Ring A, L₁, Z, R^(a), R^(b), R^(2′), R, R^(2a), R³, R¹⁰ and ‘n’        are as defined herein above.

According to another embodiment, the invention provides compounds havingthe structure of Formula (III), a stereoisomer thereof, or apharmaceutically acceptable salt thereof,

-   -   wherein,    -   Ring A, L₁, Z, R^(a), R^(b), R^(2′), R, R^(2a), R³, R¹⁰ and ‘n’        are as defined herein above.        According to one embodiment, the invention provides compounds        having the structure of Formula (IV), a stereoisomer thereof, or        a pharmaceutically acceptable salt thereof,

wherein,

X² is Br or Cl;

L₁, R^(a), R^(b), R¹, R^(2′), R², R, R^(2a) and R¹⁰ are as definedherein above.In accordance with an embodiment of the invention, R^(c) and R^(d) areindependently selected from substituted or unsubstituted alkyl or R^(c)and R^(d) together with the carbon atom to which they are attached forma cyclobutyl ring.In certain embodiment, R^(c) and R^(d) are independently selected frommethyl or R^(c) and R^(d) together with the carbon atom to which theyare attached from a cyclobutyl ring.In any of above embodiments, R^(a) and R^(b) are independently selectedfrom hydrogen, methyl, and cyclopropyl.In any of above embodiments, R³ is selected from halogen, cyano, —OR⁶,—NR⁷R⁸, substituted or unsubstituted alkyl, and substituted orunsubstituted aryl.In certain embodiments, R³ is independently selected from —F, Cl, Br,CN, —NH₂, —NH(CH₃), —NHCH(CH₃)₂, —CH₃, cyclopropyl, —CH(CH₃)₂, —CF₂CH₃,—OCH₃,

In any of above embodiments, R^(2′) and R^(2a) are independentlyselected from hydrogen and methyl.In any of above embodiments, R is selected from hydrogen, halogen,—NR⁴R⁵, and substituted or unsubstituted alkyl, substituted orunsubstituted cycloalkyl and substituted or unsubstituted heteroaryl.In certain embodiments, R is selected from hydrogen, —NH₂, methyl,Chloro, cyclopropyl, and

In any of above embodiments, R⁴ and R⁵ are independently selected fromhydrogen.In any of above embodiments, R⁶ is selected from substituted andunsubstituted alkyl.In certain embodiments, R⁶ is selected from methyl.In any of above embodiments, R⁷ and R⁸ are independently selected fromhydrogen, methyl, —CH(CH₃)₂, —CH₂-cyclopropyl, cyclopropyl, andcyclobutyl.In any of above embodiments, R¹⁰ is selected from hydrogen, —F, andmethyl.In any of above embodiments, n is selected from 1 to 3.

According to another embodiment, there are provided compounds having thestructure of Formula (I) wherein L₁ is selected from —CH₂—, —CH(CH₃)—,—NH—, —N(CH₃)— S, and O;

According to another embodiment, there are provided compounds having thestructure of Formula (I) wherein ring A is

According to another embodiment, there are provided compounds having thestructure of Formula (I) wherein ring A is

According to another embodiment, there are provided compounds having thestructure of Formula (I) wherein ring A is

According to another embodiment, there are provided compounds having thestructure of Formula (I), wherein ring A is selected from—

L1 is selected from —CH2-, —CH(CH3)-, —NH—, —N(CH3)-, S, and O; R³ isselected from F, Cl, Br, CN, —NH₂, —NH(CH₃), —NHCH(CH₃)₂, —CH₃,cyclopropyl, —CH(CH₃)₂, —CF₂CH₃, —OCH₃, CF₃,

R is selected from hydrogen, —NH₂, C1, —CH(CH₃)₂, methyl, ethyl,cyclopropyl and

R^(a) and R^(b) are independently selected from hydrogen, methyl, andcyclopropyl; R^(2′) and R^(2a) are independently selected from hydrogenand methyl; R¹⁰ is selected from hydrogen, —F, and methyl.

The examples 1 to 84 given herein are representative compounds, whichare only illustrative in nature and are not intended to limit to thescope of the invention.

It should be understood that formula (I) structurally encompasses alltautomers, stereoisomers and isotopes wherever applicable andpharmaceutically acceptable salts that may be contemplated from thechemical structures generally described herein.

According to one embodiment, there are provided compounds of formula (I)to (IV) wherein the compound is in the form of the free base or is apharmaceutically acceptable salt thereof.

In another aspect of the invention, there are provided compounds offormula (I) to (IV) or a pharmaceutically acceptable salt thereof fortreating the diseases, disorders, syndromes or conditions associatedwith PRMT5 enzyme.

In one embodiment of the present invention, there are provided compoundsof formula (I) to (IV), or a pharmaceutically acceptable salt thereoffor treating diseases, disorders, syndromes or conditions by inhibitionof PRMT5 enzyme.

In another aspect of the invention, there are provided compounds offormula (I) to (IV) or a pharmaceutically acceptable salt thereof foruse as a medicament.

In another aspect of the invention, there are provided compounds offormula (I) to (IV) or a pharmaceutically acceptable salt thereof foruse in treating the diseases, disorders, syndromes or conditionsassociated with PRMT5.

In one embodiment of the present invention, there are provided compoundsof formula (I) to (IV) or a pharmaceutically acceptable salt thereof foruse in treating diseases, disorders, syndromes or conditions by theinhibition of PRMT5.

In another aspect of the invention, there is provided a method ofinhibiting PRMT5 by using a compound selected from formula (I) to (IV)or a pharmaceutically acceptable salt thereof.

In another aspect of the invention, there is provided a method oftreating diseases, disorders or conditions associated with PRMT5 byusing a compound selected from formula (I) to (IV).

In another aspect of the present invention, a method of treatingdiseases, disorders or conditions is selected from glioblastomamultiforme, prostate cancer, and pancreatic cancer, mantle celllymphoma, non-Hodgkin's lymphomas and diffuse large B-cell lymphoma,acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma,non-small cell lung cancer, small cell lung cancer, breast cancer,triple negative breast cancer, gastric cancer, colorectal cancer,ovarian cancer, bladder cancer, hepatocellular cancer, melanoma,sarcoma, oropharyngeal squamous cell carcinoma, chronic myelogenousleukemia, epidermal squamous cell carcinoma, nasopharyngeal carcinoma,neuroblastoma, endometrial carcinoma, and cervical cancer by using acompound selected from formula (I) to (IV) is provided.

In another aspect of the invention, there is provided a use of acompound selected from formula (I) to (IV) or a pharmaceuticallyacceptable salt thereof, for the manufacture of a medicament fortreating, the diseases, disorders or conditions associated with PRMT5.

In another aspect, the invention provides a pharmaceutical compositioncomprising at least one compound of formula (I) to (IV) or apharmaceutically acceptable salt thereof and at least onepharmaceutically acceptable excipient.

In another aspect, the invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of compound of formula (I)to (IV) or a pharmaceutically acceptable salt thereof, for use intreating, the diseases, disorders or conditions associated with PRMT5 byadministering to the subject in need thereof.

In another aspect of the present invention, wherein the use of compoundsof formula (I) to (IV) or a pharmaceutically acceptable salt thereof forthe diseases, disorders, syndromes or conditions associated byinhibition of PRMT5 are selected from the group consisting ofglioblastoma multiforme, prostate cancer, and pancreatic cancer, mantlecell lymphoma, non-Hodgkin's lymphomas and diffuse large B-celllymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, multiplemyeloma, non-small cell lung cancer, small cell lung cancer, breastcancer, triple negative breast cancer, gastric cancer, colorectalcancer, ovarian cancer, bladder cancer, hepatocellular cancer, melanoma,sarcoma, oropharyngeal squamous cell carcinoma, chronic myelogenousleukemia, epidermal squamous cell carcinoma, nasopharyngeal carcinoma,neuroblastoma, endometrial carcinoma, and cervical cancer.

In another aspect, the invention provides a pharmaceutical compositioncomprising a therapeutically effective amount of compound of formula (I)to (IV) or a pharmaceutically acceptable salt thereof, for treating thediseases, disorders or conditions associated with PRMT5 by administeringto the subject in need thereof.

In another embodiment of the invention the compounds, theirstereoisomers or pharmaceutically acceptable salts thereof are:

-   (1S,2R,5R)-3-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H    pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol (Compound-1);-   (1S,2R,5R)-3-(2-(2-amino-3-chloroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-2);-   (1S,2R,5R)-3-(2-(2-amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-3);-   (1S,2R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-(((2-aminoquinolin-7-yl)thio)methyl)cyclopent-3-ene-1,2-diol    (Compound-4);-   (1S,2R,5R)-3-(((2-amino-3-chloroquinolin-7-yl)thio)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-5);-   (1S,2R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-(((2-aminoquinolin-7-yl)(methyl)amino)methyl)cyclopent-3-ene-1,2-diol    (Compound-6);-   (1S,2R,5R)-3-(1-(2-Amino-3-bromoquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-7a and 7b);-   (1S,2R,5R)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-(1-((2-(methylamino)    quinolin-7-yl)oxy)ethyl)cyclopent-3-ene-1,2-diol (Compound-8a and    8b);-   (1S,2R,5R)-3-(((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol    (Compound-9);-   (1S,2R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-(2-(2-(methylamino)quinolin-7-yl)ethyl)cyclopent-3-ene-1,2-diol    (Compound-10);-   (1S,2R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-(2-(3-methylimidazo[1,2-a]pyridin-7-yl)ethyl)cyclopent-3-ene-1,2-diol    (Compound-11);-   (1S,2R,5R)-3-(((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-4-methylcyclopent-3-ene-1,2-diol    (Compound-12);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-13);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-1H-pyrrolo[3,2-c]pyridin-1-yl)cyclopent-3-ene-1,2-diol    hydrochloride (Compound-14);-   (1S,2R,5R)-3-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(1H-pyrrolo[3,2-c]pyridin-1-yl)cyclopent-3-ene-1,2-diol    (Compound-15);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-16);-   (1S,2R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-(((2-aminoquinolin-7-yl)amino)methyl)cyclopent-3-ene-1,2-diol    (Compound-17);-   (1S,2R,5R)-3-(((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-18);-   (1S,2R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-(((2-(methylamino)quinolin-7-yl)oxy)methyl)cyclopent-3-ene-1,2-diol    (Compound-19);-   (1S,2R,5R)-3-(1-((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-20a and 20b);-   (1S,2R,5R)-3-(2-(2-amino-3-chloroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-21);-   (1S,2R,5R)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-(2-(2-(cyclobutylamino)    quinolin-7-yl)ethyl)cyclopent-3-ene-1,2-diol (Compound-22);-   (1S,2R,5R)-3-(2-(2-Amino-3-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-23);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-24);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-25);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-8-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-26);-   (1S,2R,5R)-3-(2-(2-amino-3,3-dimethyl-3H-indol-6-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-27);-   (1S,2R,5R)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3-(2-(2′-aminospiro[cyclobutane-1,3′-indol]-6′-yl)ethyl)cyclopent-3-ene-1,2-diol    (Compound-28);-   (1S,2R,5R)-3-(2-(2-amino-3,5-dichloroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-29);-   (1S,2R,5R)-3-(2-(2-amino-3-chloroquinolin-7-yl)ethyl)-5-(2-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-30);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-31);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-32);-   (1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol(Compound-33a    and 33b);-   (1S,2R,5R)-3-(1-(2-amino-3-chloroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-34a and 34b);-   (1S,2R,5R)-3-(1-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-35a and 35b);-   (1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-2-methyl-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-36a and 36b);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol    (Compound-37);-   (1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol    (Compound-38);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-2-methyl-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-39);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-ethylcyclopent-3-ene-1,2-diol    (Compound-40);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-ethyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-41);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-42);-   (1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-43);-   (1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-44);-   (1S,2R,5R)-3-(1-(2-Amino-3-bromo-5-fluoro    quinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-45a and 45b);-   (1S,2R,5R)-3-(2-(2-Amino-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-46);-   (1S,2R,5R)-3-(2-(2-amino-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-47);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-48);-   (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2-(methylamino)quinolin-7-yl)ethyl)bicyclo    [3.1.0] hexane-2,3-diol (Compound-49);-   (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2-(isopropylamino)quinolin-7-yl)ethyl)bicyclo    [3.1.0]hexane-2,3-diol (Compound-50);-   (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2-(cyclobutylamino)quinolin-7-yl)ethyl)bicyclo    [3.1.0]hexane-2,3-diol (Compound-51);-   (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2-((cyclopropylmethyl)amino)    quinolin-7-yl) ethyl)bicyclo[3.1.0]hexane-2,3-diol (Compound-52);-   (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2-amino-8-fluoroquinolin-7-yl)ethyl)bicyclo    [3.1.0]hexane-2,3-diol (Compound-53);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-methylquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)    bicyclo[3.1.0]hexane-2,3-diol (Compound-54);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-isopropyl    quinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-55);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-(1,1-difluoroethyl)    quinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo [2,3-d]    pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol (Compound-56);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-cyclopropylquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)    bicyclo[3.1.0]hexane-2,3-diol(Compound-57);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-methoxyquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-58);-   2-amino-7-(2-((1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,3-dihydroxybicyclo[3.1.0]hexan-1-yl)ethyl)quinoline-3-carbonitrile(Compound-59);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-60);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-61);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-62);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-8-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-63);-   (1R,2R,3S,4R,5S)-1-(2-(2-amino-3-bromo-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-64);-   (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(3-methylimidazo[1,2-a]pyridin-7-yl)ethyl)    bicyclo[3.1.0]hexane-2,3-diol (Compound-65);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3,3-dimethyl-3H-indol-6-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-66);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-6-methyl-7H-pyrrolo[2,3-d]    pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol (Compound-67);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-6-methyl-7H-pyrrolo[2,3-d]    pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol (Compound-68);-   (1R,2R,3S,4R,5S)-1-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-69);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-4-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-70);-   (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2′-aminospiro[cyclobutane-1,3′-indol]-6′-yl)ethyl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-71);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-72);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo    [2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol (Compound-73);-   (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2-aminoquinolin-7-yl)ethyl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-74);-   (1R,2R,3S,4R,5S)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2-aminoquinazolin-7-yl)ethyl)bicyclo[3.1.0]    hexane-2,3-diol (Compound-75);-   (1S,2R,3S,4R,5S)-1-((S)-1-(2-Amino-3-bromoquinolin-7-yl)propan-2-yl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-76a and-   76b);-   (1S,2R,3S,4R,5S)-1-((S)-2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)-1-cyclopropylethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-77a and 77b);-   (1S,2R,3S,4R,5S)-1-(1-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-78a and 78b);-   (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2-aminoquinolin-7-yl)propyl)    bicyclo[3.1.0]hexane-2,3-diol (Compound-79a and 79b);-   (1R,2R,3S,4R,5S)-1-(((2-Amino-3-bromoquinolin-7-yl)oxy)methyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-80);-   (1S,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(((2-aminoquinolin-7-yl)thio)methyl)    bicyclo [3.1.0] hexane-2,3-diol (Compound-81);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-(4-fluorophenyl)quinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol_(Compound-82);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-(pyridin-3-yl)quinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-83); and-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-(3-methyl    isoxazol-4-yl)quinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-84).-   In another embodiment of the invention the compounds, their    stereoisomer thereof, or a pharmaceutically acceptable salt thereof,    are selected from:-   (1S,2R,5R)-3-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H    pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol (Compound-1);-   (1S,2R,5R)-3-(2-(2-amino-3-chloroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-2);-   (1S,2R,5R)-3-(1-(2-Amino-3-bromoquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-7a and 7b);-   (1S,2R,5R)-3-(((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol    (Compound-9);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-13);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-1H-pyrrolo[3,2-c]pyridin-1-yl)cyclopent-3-ene-1,2-diol    hydrochloride (Compound-14);-   (1S,2R,5R)-3-(((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-18);-   (1S,2R,5R)-3-(1-((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-20a and 20b);-   (1S,2R,5R)-3-(2-(2-amino-3-chloroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-21);-   (1S,2R,5R)-3-(2-(2-Amino-3-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-23);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-24);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-25);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-8-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-26);-   (1S,2R,5R)-3-(2-(2-amino-3,5-dichloroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-29);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-31);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-32);-   (1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol(Compound-33a    and 33b);-   (1S,2R,5R)-3-(1-(2-amino-3-chloroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-34a and 34b);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol    (Compound-37);-   (1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol    (Compound-38);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-ethylcyclopent-3-ene-1,2-diol    (Compound-40);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-ethyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-41);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-42);-   (1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-43);-   (1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-44);-   (1S,2R,5R)-3-(1-(2-Amino-3-bromo-5-fluoro    quinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-45a and 45b);-   (1S,2R,5R)-3-(2-(2-Amino-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-46);-   (1S,2R,5R)-3-(2-(2-amino-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-47);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-48);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-methylquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)    bicyclo[3.1.0]hexane-2,3-diol (Compound-54);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-61);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)    bicyclo[3.1.0]hexane-2,3-diol(Compound-62);-   (1R,2R,3S,4R,5S)-1-(2-(2-amino-3-bromo-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-64);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-72); and-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo    [2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol (Compound-73).-   In another embodiment of the invention the compounds, their    stereoisomer thereof, or a pharmaceutically acceptable salt thereof,    are selected from:-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-13);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-24);-   (1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol(Compound-33a    and 33b);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol    (Compound-37);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-48);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)    bicyclo[3.1.0]hexane-2,3-diol(Compound-62);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo    [2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol (Compound-73);-   (1S,2R,5R)-3-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H    pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol (Compound-1);-   (1S,2R,5R)-3-(2-(2-amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-25);-   (1S,2R,5R)-3-(((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-18);-   (1S,2R,5R)-3-(1-(2-amino-3-chloroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-34a and 34b);-   (1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol    (Compound-38);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-61);-   (1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-43);-   (1S,2R,5R)-3-(1-(2-Amino-3-bromo-5-fluoro    quinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-45a);-   (1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol    (Compound-44);-   (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-72); and-   (1R,2R,3S,4R,5S)-1-(2-(2-amino-3-bromo-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol    (Compound-64).

DETAILED DESCRIPTION OF THE INVENTION Definitions and Abbreviations

Unless otherwise stated, the following terms used in the specificationand claims have the meanings given below.

For purposes of interpreting the specification, the followingdefinitions will apply and whenever appropriate, terms used in thesingular will also include the plural and vice versa.

The terms “halogen” or “halo” means fluorine, chlorine, bromine, oriodine.

The term “alkyl” refers to an alkane derived hydrocarbon radical thatincludes solely carbon and hydrogen atoms in the backbone, contains nounsaturation, has from one to six carbon atoms, and is attached to theremainder of the molecule by a single bond, for example (C₁-C₆)alkyl or(C₁-C₄)alkyl, representative groups include e.g., methyl, ethyl,n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl and the like.Unless set forth or recited to the contrary, all alkyl groups describedor claimed herein may be straight chain or branched.

The term “alkenyl” refers to a hydrocarbon radical containing from 2 to10 carbon atoms and including at least one carbon-carbon double bond.Non-limiting Examples of alkenyl groups include, for example(C₂-C₆)alkenyl, (C₂-C₄)alkenyl, ethenyl, 1-propenyl, 2-propenyl (allyl),iso-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl and the like.

Unless set forth or recited to the contrary, all alkenyl groupsdescribed or claimed herein may be straight chain or branched.

The term “alkynyl” refers to a hydrocarbon radical containing 2 to 10carbon atoms and including at least one carbon-carbon triple bond.Non-limiting Examples of alkynyl groups include, for example(C₂-C₆)alkynyl, (C₂-C₄)alkynyl, ethynyl, propynyl, butynyl and the like.Unless set forth or recited to the contrary, all alkynyl groupsdescribed or claimed herein may be straight chain or branched.

The term “haloalkyl” refers to an alkyl group as defined above that issubstituted by one or more halogen atoms as defined above. For example(C₁-C₆)haloalkyl or (C₁-C₄)haloalkyl. Suitably, the haloalkyl may bemonohaloalkyl, dihaloalkyl or polyhaloalkyl including perhaloalkyl. Amonohaloalkyl can have one iodine, bromine, chlorine or fluorine atom.Dihaloalkyl and polyhaloalkyl groups can be substituted with two or moreof the same halogen atoms or a combination of different halogen atoms.Suitably, a polyhaloalkyl is substituted with up to 12 halogen atoms.Non-limiting Examples of a haloalkyl include fluoromethyl,difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl,trichloromethyl, pentafluoroethyl, heptafluoropropyl,difluorochloromethyl, dichlorofluoromethyl, difluoroethyl,difluoropropyl, dichloroethyl, dichloropropyl and the like. Aperhaloalkyl refers to an alkyl having all hydrogen atoms replaced withhalogen atoms. Unless set forth or recited to the contrary, allhaloalkyl groups described or claimed herein may be straight chain orbranched.

The term “alkoxy” denotes an alkyl group attached via an oxygen linkageto the rest of the molecule. Representative examples of such groups are—OCH₃ and —OC₂H₅. Unless set forth or recited to the contrary, allalkoxy groups described or claimed herein may be straight chain orbranched.

The term “alkoxyalkyl” refers to an alkoxy group as defined abovedirectly bonded to an alkyl group as defined above, e.g., —CH₂—O—CH₃,—CH₂—O—CH₂CH₃, —CH₂CH₂—O—CH₃ and the like.

The term “cycloalkyl” refers to a non-aromatic mono or multicyclic ringsystem having 3 to 12 carbon atoms, such as (C₃-C₁₀)cycloalkyl,(C₃-C₆)cycloalkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl andthe like. Examples of multicyclic cycloalkyl groups include, but are notlimited to, perhydronaphththyl, adamantyl and norbomyl groups, bridgedcyclic groups or spirobicyclic groups, e.g., spiro(4,4)non-2-yl and thelike.

The term “aryl” refers to an aromatic radical having 6- to 14-carbonatoms, including monocyclic, bicyclic and tricyclic aromatic systems,such as phenyl, naphthyl, tetrahydronaphthyl, indanyl, and biphenyl andthe like.

The term “heterocyclic ring” or “heterocyclyl ring” or “heterocyclyl”,unless otherwise specified, refers to substituted or unsubstitutednon-aromatic 3- to 15-membered ring which consists of carbon atoms andwith one or more heteroatom(s) independently selected from N, O or S.The heterocyclic ring may be a mono-, bi- or tricyclic ring system,which may include fused, bridged or spiro ring systems and the nitrogen,carbon, oxygen or sulfur atoms in the heterocyclic ring may beoptionally oxidized to various oxidation states. In addition, thenitrogen atom may be optionally quaternized, the heterocyclic ring orheterocyclyl may optionally contain one or more olefinic bond(S), andone or two carbon atoms(S) in the heterocyclic ring or heterocyclyl maybe interrupted with —CF₂—, —C(O)—, —S(O)—, S(O)₂ etc. In additionheterocyclic ring may also be fused with aromatic ring. Non-limitingExamples of heterocyclic rings include azetidinyl, benzopyranyl,chromanyl, decahydroisoquinolyl, indolinyl, isoindolinyl, isochromanyl,isothiazolidinyl, isoxazolidinyl, morpholinyl, oxazolinyl, oxazolidinyl,2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl,octahydroindolyl, octahydroisoindolyl, perhydroazepinyl, piperazinyl,4-piperidonyl, pyrrolidinyl, piperidinyl, phenothiazinyl, phenoxazinyl,quinuclidinyl, tetrahydroisquinolyl, tetrahydrofuryl, tetrahydropyranyl,thiazolinyl, thiazolidinyl, thiamorpholinyl, thiamorpholinylsulfoxide,thiamorpholinylsulfoneindoline, benzodioxole, tetrahydroquinoline,tetrahydrobenzopyran and the like. The heterocyclic ring may be attachedby any atom of the heterocyclic ring that results in the creation of astable structure.

The term “heteroaryl” unless otherwise specified, refers to asubstituted or unsubstituted 5- to 14-membered aromatic heterocyclicring with one or more heteroatom(S) independently selected from N, O orS. The heteroaryl may be a mono-, bi- or tricyclic ring system. Theheteroaryl ring may be attached by any atom of the heteroaryl ring thatresults in the creation of a stable structure. Non-limiting Examples ofa heteroaryl ring include oxazolyl, isoxazolyl, imidazolyl, furyl,indolyl, isoindolyl, pyrrolyl, triazolyl, triazinyl, tetrazolyl,thienyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyrazinyl,pyridazinyl, benzofuranyl, benzothiazolyl, benzoxazolyl, benzimidazolyl,benzothienyl, carbazolyl, quinolinyl, isoquinolinyl, quinazolinyl,cinnolinyl, naphthyridinyl, pteridinyl, purinyl, quinoxalinyl, quinolyl,isoquinolyl, thiadiazolyl, indolizinyl, acridinyl, phenazinyl,phthalazinyl and the like.

The compounds of the present invention may have one or more chiralcenters. The absolute stereochemistry at each chiral center may be ‘R’or ‘S’. The compounds of the invention include all diastereomers andenantiomers and mixtures thereof. Unless specifically mentionedotherwise, reference to one stereoisomer applies to any of the possiblestereoisomers. Whenever the stereoisomeric composition is unspecified,it is to be understood that all possible stereoisomers are included.

The term “stereoisomer” refers to a compound made up of the same atomsbonded by the same bonds but having different three-dimensionalstructures which are not interchangeable. The three-dimensionalstructures are called configurations. As used herein, the term“enantiomer” refers to two stereoisomers whose molecules arenon-superimposable mirror images of one another. The term “chiralcenter” refers to a carbon atom to which four different groups areattached. As used herein, the term “diastereomers” refers tostereoisomers which are not enantiomers. The terms “racemate” or“racemic mixture” refer to a mixture of equal parts of enantiomers.

A “tautomer” refers to a compound that undergoes rapid proton shiftsfrom one atom of the compound to another atom of the compound. Some ofthe compounds described herein may exist as tautomers with differentpoints of attachment of hydrogen. The individual tautomers as well asmixture thereof are encompassed with compounds of formula (I).

The term “treating” or “treatment” of a state, disorder or conditionincludes: (a) preventing or delaying the appearance of clinical symptomsof the state, disorder or condition developing in a subject that may beafflicted with or predisposed to the state, disorder or condition butdoes not yet experience or display clinical or subclinical symptoms ofthe state, disorder or condition; (b) inhibiting the state, disorder orcondition, i.e., arresting or reducing the development of the disease orat least one clinical or subclinical symptom thereof; c) lessening thedisease, disorder or condition or at least one of its clinical orsubclinical symptoms or (d) relieving the disease, i.e., causingregression of the state, disorder or condition or at least one of itsclinical or subclinical symptoms.

The term “inhibitor” refers to a molecule that binds to an enzyme toinhibit the activity of the said enzyme either partially or completely.

The term “subject” includes mammals (especially humans) and otheranimals, such as domestic animals (e.g., household pets including catsand dogs) and non-domestic animals (such as wildlife).

A “therapeutically effective amount” means the amount of a compoundthat, when administered to a subject for treating a disease, disorder orcondition, is sufficient to cause the effect in the subject, which isthe purpose of the administration. The “therapeutically effectiveamount” will vary depending on the compound, the disease and itsseverity and the age, weight, physical condition and responsiveness ofthe subject to be treated.

Pharmaceutically Acceptable Salts

The compounds of the invention may form salts with acid or base. Thecompounds of invention may be sufficiently basic or acidic to formstable nontoxic acid or base salts, administration of the compound as apharmaceutically acceptable salt may be appropriate. Non-limitingExamples of pharmaceutically acceptable salts are inorganic, organicacid addition salts formed by addition of acids including hydrochloridesalts. Non-limiting Examples of pharmaceutically acceptable salts areinorganic, organic base addition salts formed by addition of bases. Thecompounds of the invention may also form salts with amino acids.Pharmaceutically acceptable salts may be obtained using standardprocedures well known in the art, for example by reacting sufficientlybasic compound such as an amine with a suitable acid.

Screening of the compounds of invention for PRMT5 inhibitory activitycan be achieved by using various in vitro and in vivo protocolsmentioned herein below or methods known in the art.

Pharmaceutical Compositions

The invention relates to pharmaceutical compositions containing thecompounds of the formula (I), or pharmaceutically acceptable saltsthereof disclosed herein. In particular, pharmaceutical compositionscontaining a therapeutically effective amount of at least one compoundof formula (I) described herein and at least one pharmaceuticallyacceptable excipient (such as a carrier or diluent). Preferably, thecontemplated pharmaceutical compositions include the compound(s)described herein in an amount sufficient to inhibit PRMT5 to treat thediseases described herein when administered to a subject.

The subjects contemplated include, for example, a living cell and amammal, including human. The compound of the invention may be associatedwith a pharmaceutically acceptable excipient (such as a carrier or adiluent) or be diluted by a carrier, or enclosed within a carrier whichcan be in the form of a capsule, sachet, paper or other container. Thepharmaceutically acceptable excipient includes pharmaceutical agent thatdoes not itself induce the production of antibodies harmful to theindividual receiving the composition, and which may be administeredwithout undue toxicity.

Examples of suitable carriers or excipients include, but are not limitedto, water, salt solutions, alcohols, polyethylene glycols,polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin,lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar,cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin,acacia, stearic acid or lower alkyl ethers of cellulose, salicylic acid,fatty acids, fatty acid amines, fatty acid monoglycerides anddiglycerides, pentaerytritol fatty acid esters, polyoxyethylene,hydroxymethylcellulose and polyvinylpyrrolidone.

The pharmaceutical composition may also include one or morepharmaceutically acceptable auxiliary agents, wetting agents,emulsifying agents, suspending agents, preserving agents, salts forinfluencing osmotic pressure, buffers, sweetening agents, flavoringagents, colorants, or any combination of the foregoing. Thepharmaceutical composition of the invention may be formulated so as toprovide quick, sustained, or delayed release of the active ingredientafter administration to the subject by employing procedures known in theart.

The pharmaceutical compositions described herein may be prepared byconventional techniques known in the art. For example, the activecompound can be mixed with a carrier, or diluted by a carrier, orenclosed within a carrier, which may be in the form of an ampoule,capsule, sachet, paper, or other container. When the carrier serves as adiluent, it may be a solid, semi-solid, or liquid material that acts asa vehicle, excipient, or medium for the active compound. The activecompound can be adsorbed on a granular solid container, for Example, ina sachet.

The pharmaceutical compositions may be in conventional forms, forexample, capsules, tablets, caplets, orally disintegrating tablets,aerosols, solutions, suspensions or products for topical application.

The route of administration may be any route which effectivelytransports the active compound of the invention to the appropriate ordesired site of action. Suitable routes of administration include, butare not limited to, oral, oral inhalation, nasal, pulmonary, buccal,subdermal, intradermal, transdermal, parenteral, rectal, depot,subcutaneous, intravenous, intraurethral, intramuscular, intranasal,ophthalmic (such as with an ophthalmic solution) or topical (such aswith a topical ointment).

Solid oral formulations include, but are not limited to, tablets,caplets, capsules (soft or hard gelatin), orally disintegrating tablets,dragees (containing the active ingredient in powder or pellet form),troches and lozenges. Tablets, dragees, or capsules having talc and/or acarbohydrate carrier or binder or the like are particularly suitable fororal application. Liquid formulations include, but are not limited to,syrups, emulsions, suspensions, solutions, soft gelatin and sterileinjectable liquids, such as aqueous or non-aqueous liquid suspensions orsolutions. For parenteral application, particularly suitable areinjectable solutions or suspensions, preferably aqueous solutions withthe active compound dissolved in polyhydroxylated castor oil.

The pharmaceutical preparation is preferably in unit dosage form. Insuch form the preparation is subdivided into unit doses containingappropriate quantities of the active component. The unit dosage form canbe a packaged preparation, the package containing discrete quantities ofpreparation, such as pocketed tablets, capsules, and powders in vials orampoules. Also, the unit dosage form can be a capsule, tablet, caplet,cachet, or lozenge itself, or it can be the appropriate number of any ofthese in packaged form.

For administration to subject patients, the total daily dose of thecompounds of the invention depends, of course, on the mode ofadministration. For example, oral administration may require a highertotal daily dose, than an intravenous (direct into blood). The quantityof active component in a unit dose preparation may be varied or adjustedfrom 0.1 mg to 1000 mg by oral administration and 1 μg to 5000 μg byinhalation according to the potency of the active component or mode ofadministration.

Those skilled in the relevant art can determine suitable doses of thecompounds for use in treating the diseases and disorders describedherein. Therapeutic doses are generally identified through a doseranging study in subject based on preliminary evidence derived from theanimal studies. Doses must be sufficient to result in a desiredtherapeutic benefit without causing unwanted side effects for thepatient. For example, the daily dosage of the PRMT5 inhibitor can rangefrom about 0.1 to about 30.0 mg/kg by oral administration. Mode ofadministration, dosage forms, suitable pharmaceutical excipients,diluents or carriers can also be well used and adjusted by those skilledin the art. All changes and modifications envisioned are within thescope of the invention.

Methods of Treatment

The invention provides compound of formula (I) and pharmaceuticalcompositions thereof as protein arginine methyl transferase-5 (PRMT5)inhibitors for treating the diseases, disorders or conditions associatedwith overexpression of PRMT5. The invention further provides a method oftreating diseases, disorders or conditions associated withoverexpression of PRMT5 in a subject in need thereof by administering tothe subject a therapeutically effective amount of a compound or apharmaceutical composition of the invention.

In another aspect, the invention relates to a method of treatingdiseases, disorders or conditions associated with the overexpression ofPRMT5. In this method, a subject in need of such treatment isadministered a therapeutically effective amount of a compound of formula(I) or a pharmaceutically acceptable salt thereof as described herein.

In one embodiment of the present invention, the diseases, disorders, orconditions associated with the overexpression of PRMT5 are cancer.

In another embodiment, the invention provides a method of treatingcancers, particularly, glioblastoma multiforme, prostate cancer,pancreatic cancer, mantle cell lymphoma, non-Hodgkin's lymphomas anddiffuse large B-cell lymphoma, acute myeloid leukemia, acutelymphoblastic leukemia, multiple myeloma, non-small cell lung cancer,small cell lung cancer, breast cancer, triple negative breast cancer,gastric cancer, colorectal cancer, ovarian cancer, bladder cancer,hepatocellular cancer, melanoma, sarcoma, oropharyngeal squamous cellcarcinoma, chronic myelogenous leukemia, epidermal squamous cellcarcinoma, nasopharyngeal carcinoma, neuroblastoma, endometrialcarcinoma, and cervical cancer.

It is to be understood that the invention encompasses the compounds offormula (I) or pharmaceutically acceptable salts thereof for use in thetreatment of a disease or disorder mentioned herein.

It is to be understood that the invention encompasses the compounds offormula (I) or pharmaceutically acceptable salts thereof in themanufacture of a medicament for treating a disease or disorder mentionedherein.

General Methods of Preparation

The compound of formula described herein may be prepared by techniquesknown in the art. In addition, the compound of formula described hereinmay be prepared by following the reaction sequence as depicted inScheme-1 to Scheme-27. Further, in the following schemes, where specificbases, acids, reagents, solvents, coupling agents, etc., are mentioned,it is understood that other bases, acids, reagents, solvents, couplingagents etc., known in the art may also be used and are thereforeincluded within the scope of the present invention. Variations inreaction conditions, for example, temperature and/or duration of thereaction, which may be used as known in the art, are also within thescope of the present invention. All the isomers of the compound offormula in described in these schemes, unless otherwise specified, arealso encompassed within the scope of this invention.

Scheme-1 illustrates the synthesis of compound of formula 10 (when Q¹ isN, CH or CX, where X can be Cl or Br). Compound of formula 1 (wherePG=Protecting group), is prepared by following the procedure reported inKenneth A. Jacobson et. al; Purinergic Signalling (2015) 11:371-387.Mitsunobu reaction of compound of formula 1 with compound of formula 2(X=—Cl, —Br) using various azo dicarboxylate reagents such as but notlimited to DEAD or DIAD in presence of phosphine such as but not limitedto PPh₃ to form the compound of formula 3. Compound of formula 4 isformed upon treatment of compound of formula 3 with fluoride ions suchas but not limited to TBAF. Oxidation of compound of formula 4 withoxidising agents such as but not limited to Dess-Martin periodinane canfurnish the compound of formula 5. Reagents such as but not limited tomethyltriphenylphosphonium bromide in presence of a base such as but notlimited to KO^(t)Bu, NaO^(t)Bu, LiHMDS, NaHMDS, or KHMDS when treatedwith compound of formula 5 affords compound of formula 6. Compound offormula 6a (where R⁴ and R⁵ are defined herein above) upon treatmentwith compound of formula 6 affords compound of formula 7. Compound offormula 9 can be achieved by hydroboration of compound of formula 7 withsuitable boranes such as but not limited to 9-BBN followed by additionof inorganic base such as but not limited to K₃PO₄ or Cs₂CO₃, inpresence of Pd catalyst such as but not limited to Pd(dppf)Cl₂ orPd(PPh₃)₂Cl₂ and compound of formula 8 (Y=—Br, —I, which can be preparedby following the procedure reported J. Med. Chem., 2017, 60 (9),3958-3978). Acetonide deprotection of compound of formula 9 with acidssuch as but not limited to HCl or TFA affords compound of formula 10.

Scheme-2 illustrates the synthesis of compound of formula 16. This canbe achieved by Mitsunobu reaction of compound of formula 1a, which isprepared by following the procedure reported in Kenneth A. Jacobson et.al; Purinergic Signalling (2015) 11:371-387, with compound of formula 2using various azo dicarboxylate reagents such as but not limited to DIADin presence of phosphine such as but not limited to PPh₃ to form thecompound of formula 11, which can be further converted to compound offormula 12 upon treatment with fluoride ions such as but not limited toTBAF. Mitsunobu reaction of compound of formula 12 with compound offormula 13 (commercially available or synthesized as per knownliterature, where Q¹=C or N, R³, R⁷ and R⁸ are defined herein above)using various azo dicarboxylate reagents such as but not limited to DIADin presence of phosphine such as but not limited to PPh₃ affords thecompound of formula 14. Compound of formula 6a upon treatment withcompound of formula 14 affords compound of formula 15. Acetonidedeprotection of compound of formula 15 with acids such as but notlimited to HCl or TFA affords compound of formula 16.

Scheme-3 illustrates the synthesis of compound of formula 21. Compoundof formula 17 is formed upon treatment of compound of formula 12 withoxidising agents such as but not limited to Dess-Martin periodinane.Reagents such as but not limited to methyltriphenylphosphonium bromidein presence of a base such as but not limited to KOBu, NaOBu, LiHMDS,NaHMDS, or KHMDS when treated with compound of formula 17 affordscompound of formula 18. Compound of formula 19 can be synthesized byhydroboration of compound of formula 18 with suitable boranes such asbut not limited to 9-BBN followed by addition of inorganic base such asbut not limited to tripotassium phosphate or Cs₂CO₃, in presence of Pdcatalyst such as but not limited to Pd(dppf)Cl₂ or Pd(PPh₃)₂Cl₂ andcompound of formula 8 (Y=—Br, —I), which was synthesized by followingthe procedure reported in WO2012002577 A1, followed by N-oxideformation, chlorination with phosphoroxychloride and nucleophilicsubstitution with PMB-NH₂ or J. Med. Chem, 2017, 60 (9), 3958-3978).Compound of formula 6a (where R⁴ and R⁵ are defined herein above) upontreatment with compound of formula 19 affords compound of formula 20.Acetonide deprotection of compound of formula 20 with acids such as butnot limited to HCl or TFA affords compound of formula 21.

Scheme-4 illustrates the synthesis of compound of formula 27. Compoundof formula 22 is formed upon treatment of compound of formula 5 withGrignard reagent such as but not limited to methylmagnesium bromide,ethylmagnesium bromide, cyclopropylmagnesium bromide etc. Compound offormula 22 on oxidation with oxidising agents such as but not limited toDess-Martin periodinane gives compound of formula 23. Reagents such asbut not limited to methyltriphenylphosphonium bromide in presence ofbase such as but not limited to KOBu, NaOBu, LiHMDS, NaHMDS, or KHMDSwhen treated with compound of formula 23 affords compound of formula 24.Compound of formula 25 can be achieved by hydroboration of compound offormula 24 with suitable boranes such as but not limited to 9-BBNfollowed by addition of inorganic base such as but not limited totripotassium phosphate or Cs₂CO₃, in presence of Pd catalyst such as butnot limited to Pd(dppf)Cl₂ or Pd(PPh₃)₂Cl₂ and compound of formula 8(Y=—Br, —I), which was synthesized by following the procedure reportedin WO2012002577 A1, followed by N-oxide formation, chlorination withPhosphoroxychloride, and nucleophilic substitution with PMB-NH₂ or J.Med. Chem, 2017, 60 (9), 3958-3978). Compound of formula 6a (where R₄and R₅ are defined herein above) upon treatment with compound of formula25 affords compound of formula 26. Acetonide deprotection of compound offormula 26 with acids such as but not limited to HCl or TFA affordscompound of formula 27.

Scheme-5 illustrates the synthesis of compound of formula 32. Compoundof formula 28 is formed upon treatment of compound of formula 5 withWittig reagents such as but not limited to (1-iodoethyl)triphenylphosphonium bromide. Compound of formula 29 can be achieved bySuzuki coupling of compound of formula 28 with suitable inorganic basesuch as but not limited to tripotassium phosphate or Cs₂CO₃, in presenceof Pd catalyst such as but not limited to Pd(PPh₃)₄, Pd(dppf)Cl₂ orPd(PPh₃)₂Cl₂ and compound of formula 8a (Y=—Br, —I). Compound of formula6a (where R⁴ and R⁵ are defined herein above) upon treatment withcompound of formula 29 affords compound of formula 30. Hydrogenation ofcompound of formula 30 affords compound of formula 31. Acetonidedeprotection of compound of formula 31 with acids such as but notlimited to HCl or TFA affords compound of formula 32.

Compound of formula-33 (can be synthesized by following the protocol asmentioned in Med. Chem. Comm.; vol. 4; nb. 5; (2013); p. 822-826) upontreatment with iodine in presence of pyridine affords Compound offormula-34, which can be reduced by cerium chloride and sodiumborohydride to get compound of formula-35. Mitsunobu reaction usingcompound of formula-2 with compound of formula-35 provides the compoundof formula-36. Halogen of compound of formula-36 on substitution withPMB amine, followed by Suzuki reaction affords the compound offormula-38. TBDMS deprotection of compound of formula-38 followed bytosylation of compound of formula-39 provides compound of formula-40.The tosyl of compound of formula-40 is replaced with compound offormula-13 gives the compound of formula-41, which is furtherdeprotected in acidic condition to get the final compound of formula-42.

Reaction of compound of formula-43 [can be prepared by method reportedin J. Org. Chem. 2014. 79. 8059-8066] with methyl magnesium bromidegives compound of formula-44, with only one stereoisomer with goodyield. This when subjected to acetonide shuffling affords compound offormula-46. Mitsunobu reaction using compound of formula 2 with compoundof formula-46 yields the compound of formula-47, which can be convertedto compound of formula-48 on treating with TBAF. Compound of formula-48can be oxidized with DMP to afford Compound of formula-49, which canundergo Witting reaction to give compound of formula-50. Compound offormula 51 can be achieved by hydroboration of compound of formula 50with suitable boranes such as but not limited to 9-BBN followed byaddition of inorganic base such as but not limited to K₃PO₄ or Cs₂CO₃,in presence of Pd catalyst such as but not limited to Pd(dppf)Cl₂ orPd(PPh₃)₂Cl₂ and compound of formula 8. Compound of formula-51 ontreating with aq. ammonia followed by treatment with trifluroacetic acidaffords compound of formula-53.

Compound of formula-48 (compound of formula 48a can be synthesized from48 by oxidation and Grignard reaction) when condensed with compound offormula-13 using Mitsunobu reaction affords compound of formula-54,which can be reacted with ammonia followed by treatment withtrifluroacetic acid to provide a compound of formula 56.

6-Halo-oxindole on treatment with a base, and methyl iodide ordiiodopropane or appropriately substituted dihalide provides compound offormula-57. Compound of formula 57 when treated with Lawesson's reagentin hydrocarbon solvent such as but not limited to toluene at 100° C. for3 h gives compound of formula-58, which is then treated with sodiumhydride followed by methyl iodide in THF to yield compound of formula59. Compound of formula 59 on treating with 7N ammonia in methanol at100° C. for 16 h provides compound of formula-60.

Hydroboration of compound of formula-18 with 9-BBN followed Suzukicoupling with compound of formula-59 in presence of Pd-118 or PdCl₂dppfin THF/H₂O at 50-70° C. for 5-16 h provide compound of formula-61, whichis then treated with compound of formula-6a followed by TFA to givecompound of formula 63.

Hydroboration of compound of formula-7 with 9-BBN followed Suzukicoupling with compound of formula-59 in presence of Pd-118 or PdCl₂dppfin THF/H₂O at 50-70° C. for 5-16 h affords compound of formula-64, whichis then treated with compound of formula-6a followed by TFA to affordcompound of formula 66.

Hydroboration of compound of formula-18 with 9-BBN followed Suzukicoupling with compound of formula-67 in presence of Pd-118 in THF/H₂O at50° C. for 5-16 h affords compound of formula-68, which is when treatedwith compound of formula-6a followed by TFA affords compound offormula-70. Hydroboration of compound of formula-7 with 9-BBN followedSuzuki coupling with compound of formula-67 in presence of Pd-118 orPdCl₂dppf in THF/H₂O at 50-70° C. for 5-16 h affords compound offormula-71, which is when treated with TFA affords compound offormula-72.

Hydroboration of compound of formula-6 with 9-BBN followed by Suzukicoupling of compound of formula 8 in presence of Pd-118 or PdCl₂dppf inTHF/H₂O at 50-70° C. for 5-16 h affords compound of formula 73, which iswhen treated with compound of formula-6a followed by treatment with TFAaffords compound of formula 75.

Compound of formula-17 when treated with methylmagnesium bromide in THFgives compound of formula-76, which can be oxidized by DMP in methylenechloride at 0° C. to afford compound of formula-77. Addition ofmethylmagnesium bromide on compound of formula-77 provides compound offormula-78. Dehydration of compound of formula-78 with Martin Sulfuranegives compound of formula-79, which then treated with 9-BBN followed bySuzuki coupling with compound of formula-8 in presence of Pd-118 orPdCl₂dppf in THF/H₂O at 50-70° C. for 5-16 h affords compound offormula-80. Treating compound of formula-80 with compound of formula 6afollowed by treatment with TFA affords compound of formula-82.

Compound of formula-11 on treatment with trimethylboroxine in presenceof tripotassium phosphate, and Pd-118 or PdCl₂dppf gives mixture ofcompound of formula-83 and compound of formula-84. The PG of compound offormula-83 can be deprotected to afford compound of formula-85, which onoxidation with DMP gives compound of formula-86. Wittig reaction ofcompound of formula-86 provides compound of formula-87. Hydroboration ofcompound of formula-87 with 9-BBN followed by Suzuki coupling withcompound of formula-8 in presence of Pd-118 or PdCl₂dppf in THF/H₂O at50-70° C. for 5-16 h affords compound of formula-88, which when treatedwith TFA affords compound of formula-89.

The protecting group of compound of formula-84 can be deprotected toafford compound of formula-90, which on oxidation with DMP givescompound of formula-91. Wittig reaction of compound of formula-91provides compound of formula-92. Hydroboration of compound of formula-92with 9-BBN followed by Suzuki coupling with compound of formula-8 inpresence of Pd-118 or PdCl₂dppf in THF/H₂O at 50-70° C. for 5-16 haffords compound of formula-93, which is then treated with TFA to affordcompound of formula 94.

Reductive amination of compound of formula-17 with compound offormula-95 affords compound of formula-96, which is then treated withcompound of formula-6a followed by treatment with TFA to afford compoundof formula-98.

Compound of formula-12 is treated with TsCl/MSCl in presence of a baseto give a compound of formula-99, which is then reacted with compound offormula-100 to yield compound of formula-101. Reaction of compound offormula-101 with compound of formula-6a followed by treatment with TFAaffords compound of formula-103.

Compound of formula-99 is reacted with compound of formula-104 inpresence of a base such as but not limited to cesium carbonate to afforda compound of formula-105. Substitution reaction of compound offormula-105 with compound of formula-6a followed by treatment with TFAaffords compound of formula-107.

The compound of formula-109 can be synthesized by Mitsunobu reaction ofcompound of formula 1a with compound of formula 108 using various azodicarboxylate reagents such as but not limited to DIAD in presence ofphosphine such as but not limited to PPh₃. Compound of formula-109 canbe further converted to compound of formula 110 upon treatment withfluoride ions such as but not limited to TBAF. Oxidation followed byWittig reaction on compound of formula 110 gives compound of formula112. The aromatic halogen of compound of formula 112 can be converted toalkyl groups such as a methyl group using Pd-118 or PdCl₂dppf withtrimethylboroxine to afford compound of formula 113. Hydroboration ofcompound of formula-113 with 9-BBN followed by Suzuki coupling withcompound of formula-8 in presence of Pd-118 or PdCl₂dppf in THF/H₂O at50-70° C. for 5-16 h affords compound of formula-114, which when treatedwith TFA or HCl/MeOH affords compound of formula-115.

Mitsunobu reaction of compound of formula 4 (can be prepared fromcompound of formula 1 as described in scheme 1) with compound of formula13 using various azo dicarboxylate reagents such as but not limited toDIAD in presence of phosphine such as but not limited to PPh₃ providescompound of formula 116. Compound of formula-116 on treating compound offormula 6a followed by treatment with trifluroacetic acid affordscompound of formula-118.

Scheme-22 illustrates the synthesis of compound of formula 126. Compoundof formula 119 (where PG=Protecting group), is prepared by Simmon Smithreaction. Mitsunobu reaction of compound of formula 119 with compound offormula 2 (X=—Cl, —Br) using various azo dicarboxylate reagents such asbut not limited to DEAD or DIAD in presence of phosphine such as but notlimited to PPh₃ to form the compound of formula 120. Compound of formula121 is formed upon treatment of compound of formula 120 with fluorideions such as but not limited to TBAF. Oxidation of compound of formula121 with oxidising agents such as but not limited to Dess-Martinperiodinane can furnish the compound of formula 122. Reagents such asbut not limited to me thyltriphenylphosphonium bromide in presence of abase such as but not limited to KOtBu, NaOtBu, LiHMDS, NaHMDS, or KHMDSwhen treated with compound of formula 122 affords compound of formula123. Amine of formula 6a (where R₄ and R₅ are defined herein above) upontreatment with compound of formula 123 affords compound of formula 124.Compound of formula 125 can be achieved by hydroboration of compound offormula 124 with suitable boranes such as but not limited to 9-BBNfollowed by addition of inorganic base such as but not limited to K₃PO₄or Cs₂CO₃, in presence of Pd catalyst such as but not limited toPd(dppf)Cl₂ or Pd(PPh₃)₂Cl₂ and compound of formula 8 (Y=—Br, —I, whichcan be prepared by following the procedure reported J. Med. Chem., 2017,60 (9), 3958-3978). Acetonide deprotection of compound of formula 125with acids such as but not limited to HCl or TFA affords compound offormula 126.

Suzuki coupling of compound of formula 10 with aryl or heteroarylboronic acid or ester in presence of Pd(PPh₃)₄ or Pd-118 or PdCl₂dppf indioxane at 80-100° C. for 5-16 h affords compound of formula-127.

Compound of formula-18 when treated with compound of formula-128 usingSuzuki coupling affords compound of formula-129. Compound of formula 130can be achieved by hydroboration of compound of formula 129 withsuitable boranes such as but not limited to 9-BBN followed by additionof inorganic base such as but not limited to K₃PO₄ or Cs₂CO₃, inpresence of Pd catalyst such as but not limited to Pd(dppf)Cl₂ orPd(PPh₃)₂Cl₂ and compound of formula 8 (Y=—Br, —I, which can be preparedby following the procedure reported J. Med. Chem., 2017, 60 (9),3958-3978). Acetonide deprotection of compound of formula 130 with acidssuch as but not limited to HCl or TFA affords compound of formula 131.

Compound of formula-76 when condensed with compound of formula-13 usingMitsunobu reaction affords compound of formula-132, which can be reactedwith compound of formula-6a followed by treatment with trifluroaceticacid to provide a compound of formula-134.

Compound of formula-48a when treated DMP in methylene chloride at 0° C.to afford compound of formula-135, which when react with methylmagnesiumbromide in THF gives compound of formula-136. Dehydration of compound offormula-136 with Martin Sulfurane gives compound of formula-137, whichthen treated with 9-BBN followed by Suzuki coupling with compound offormula-8 in presence of Pd-118 or PdCl₂dppf in THF/H₂O at 50-70° C. for5-16 h affords compound of formula-138. Treating compound of formula-138with compound of formula 6a followed by treatment with TFA affordscompound of formula-140.

Compound of formula-4 is treated with TsCl/MSCl in presence of a base togive a compound of formula 141. Compound of formula-141 is reacted withcompound of formula-104 in presence of a base such as but not limited tocesium carbonate to afford a compound of formula-142. Substitutionreaction of compound of formula-142 with compound of formula-6a followedby treatment with TFA affords compound of formula-144.

Abbreviations

The following abbreviations may be used herein:

AcOH=Acetic acid

Aq.=aqueous

ca=about or approximately

NH₄Cl=Ammonium chloride

9-BBN=9-Borabicyclononane

BINAP=2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl

Boc=tert-Butoxycarbonyl

t-Bu or tBu=tert-Butyl

Cs₂CO₃=Cesium Carbonate

CHCl₃=Chloroform

CDCl₃=Deuterated chloroform

DAST=Diethylaminosulphur trifluoride

dba=Dibenzylideneacetone

CH₂Cl₂ or DCM=Dichloromethane

DMP=Dess Martin Periodinane

DEAD=Diethyl azodicarboxylate

DIAD=Diisopropyl azodicarboxylate

DIPEA=Diisopropylethylamine

DMAP=4-Dimethylaminopyridine

DMF=N,N-Dimethylformamide

DMSO=Dimethylsulphoxide

DMSO-d₆=Deuterated dimethylsulphoxide

Et=ethyl

EtOH=Ethanol

EtOAc=Ethyl acetate

g=gram

H₂O₂=Hydrogen peroxide

H₂SO₄=Sulphuric acid

K₂CO₃=Potassium carbonate

KOH=Potassium hydroxide

KOtBu=Potassium tert-butoxide

K₃PO₄=Potassium phosphate

KHMDS=Potassium bis(trimethylsilyl)amide

LDA=Lithium diisopropylamide

LHMDS=Lithium bis(trimethylsilyl)amide

LCMS=Liquid chromatography mass spectrometry

m-CPBA=meta-chloroperoxybenzoic acid

mg=milligram

Me=Methyl

MeOH=Methanol

MeOD=Deuterated methanol

MS=Molecular sieves

MsCl=Methanesulphonyl chloride

MgSO₄=Magnesium sulphate

NaH=Sodium hydride

NaOtBu=Sodium tert-butoxide

NaHCO₃=Sodium bicarbonate

Na₂SO₄=Sodium sulphate

Na₂S₂O₃=Sodium thiosulphate

Na₂SO₃=Sodium sulphite

NaHMDS=Sodium bis(trimethylsilyl)amide

NMP=N-Methyl-2-pyrrolidone

NBS=N-Bromosuccinimide

NCS=N-Chlorosuccinimide

NIS=N-Iodosuccinimide

NMO=N-Methylmorpholine-N-oxide

NMR=Nuclear magnetic resonance

Ph=phenyl

PDC=Pyridinium dichlorochromate

Pd(OAc)₂=Palladium acetate

Pd/C=Palladium on carbon

Pd-118=[1,1′-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II)

Pd(PPh₃)₄=Tetrakis(triphenylphosphine)palladium(0)

POCl₃=Phosphorous oxychloride

PdCl₂(dppf)=[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)

Pd(PPh₃)₂Cl₂=Bis(triphenylphosphine)palladium(II) dichloride

PCC=Pyridinium chlorochromate

PMB=p-Methoxybenzyl

PTSA=p-Toluenesulphonic acid

Rt=Retention time

rt=room temperature

Sat.=saturated

SFC=Supercritical fluid chromatography

TLC=Thin layer chromatography

TBAF=Tetrabutylammonium fluoride

TsCl=p-Toluenesulphonyl chloride

TBDMS=tert-Butyldimethylsilyl

TBDPS=tert-Butyldiphenylsilyl

Et₃N or NEt₃ or TEA=Triethylamine

TFA=Trifluoroacetic acid

THF=Tetrahydrofuran

Ts=p-Toluenesulphonyl

p-TsOH=p-Toluenesulphonic acid

INTERMEDIATES 7-Bromoquinolin-2-amine

The title compound was prepared by following an analogous reactionprotocol as described in Cinelli, Maris A et al, Journal of MedicinalChemistry, 2017, vol. 60, #9, p. 3958-3978.

7-Bromo-N-(4-methoxybenzyl)quinolin-2-amine

The title compound was prepared by following an analogous reactionprotocol as described in Arnould, Jean-Claude et al, WO 2007/141473 A1.

7-Bromo-N-methylquinolin-2-amine

The title compound was prepared by following same reaction protocol asdescribed in Arnould, Jean-Claude et al, WO 2007/141473 A1.

7-Bromo-N-isopropylquinolin-2-amine

The title compound was prepared by following an analogous reactionprotocol as described in Arnould, Jean-Claude et al, WO 2007/141473 A1.

7-Bromo-N-cyclobutylquinolin-2-amine

The title compound was prepared by following an analogous reactionprotocol as described in Arnould, Jean-Claude et al, WO 2007/141473 A1.

7-Bromo-N-(cyclopropylmethyl)quinolin-2-amine

The title compound was prepared by following analogous reaction protocolas described in Arnould, Jean-Claude et al, WO 2007/141473 A1.

7-Bromo-2-chloro-8-fluoroquinoline

The title compound was prepared by following same reaction protocol asdescribed in Aciro, Caroline et al, WO2013/185103 A1.

7-Bromo-2-chloro-3-isopropylquinoline

The title compound was prepared by following same reaction protocol asdescribed in Vialard, Jorge Eduardo et al, WO2008/107478 A1; LCMSm/z=284.1, 286.1 (M+, M+2; 100%).

2-Amino-4-bromo-6-fluorobenzaldehyde

To a stirred solution of 4-bromo-2-fluoro-6-nitrobenzaldehyde (preparedby following same reaction protocol as described in Li, Liansheng et al,WO 2015/054572 A1; 4.15 g, 16.73 mmol) in ethanol (20 ml) & acetic acid(20 ml) was added iron powder (2.80 g, 50.2 mmol) at 0° C. and stirredthe reaction mixture for 1 h. The reaction mixture was diluted withethyl acetate (70 ml) and netralized with aq. sat. NaHCO₃ (100 ml). Theresulting emulsion was filtered through celite. Layers were separated,organic layer was washed with brine (100 ml) and dried over anhydrousNa₂SO₄. The organic layer was filtered and concentrated in vacuo toafford (3.36 g, 92%) as a light green solid which was used for next stepwithout purification. ¹H NMR (400 MHz, DMSO-d₆) δ 10.10 (s, 1H),7.78-7.54 (m, 2H), 6.84 (t, J=1.5 Hz, 1H), 6.64 (dd, J=11.1, 1.8 Hz,1H).

1-Chloro-5-iodo-2-methyl-3-nitrobenzene

A solution of iodine (10.43 g, 41.1 mmol), potassium iodate (1.247 g,5.83 mmol) in conc. H₂SO₄ (51.4 g, 525 mmol) was added to a solution of1-chloro-2-methyl-3-nitrobenzene (5 g, 29.1 mmol) in conc. H₂SO₄ (51.4g, 525 mmol) at 25° C. The resulting mixture was stirred at 25° C. for 6h. The reaction mixture was added slowly onto crushed ice and extractedthe product with ethyl acetate (75 ml). The organic layer was washedwith aq.sat.NaHCO₃ (75 ml), aq.sat.Na₂S₂O₃ (75 ml) and brine (75 ml)successively. Dried the organic layer over anhydrous Na₂SO₄, filteredand concentrated in vacuo to give 9 g of crude compound. This residuewas purified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with elution of petroleum ether to afford thetitle compound (8.5 g, 98%) as a pale yellow oil. ¹H NMR (400 MHz,Chloroform-d) δ 8.02 (d, J=1.4 Hz, 1H), 7.96 (d, J=1.7 Hz, 1H), 2.50 (s,3H).

2-(Bromomethyl)-1-chloro-5-iodo-3-nitrobenzene

To a stirred solution of 1-chloro-5-iodo-2-methyl-3-nitrobenzene (27.5g, 92 mmol) in CCl₄ (280 ml) was added NBS (19.74 g, 111 mmol) andbenzoyl peroxide (2.99 g, 9.24 mmol) at 25° C. The resulting mixture wasstirred at 80° C. for 15 h. The solvent was evaporated in vacuo and thisresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution of (0 to 1%) of ethylacetate in petroleum ether to afford the title compound (12 g, 34.5%) asan off-white solid. H NMR (400 MHz, DMSO-d₆) δ 8.37-8.33 (m, 2H), 4.72(s, 2H).

2-Chloro-4-iodo-6-nitrobenzaldehyde

To a stirred solution of 2-(bromomethyl)-1-chloro-5-iodo-3-nitrobenzene(12 g, 31.9 mmol) in acetonitrile (150 ml) was added4-methylmorpholine-N-oxide (9.19 g, 78 mmol) and molecular sieves 4A°(30 g) at 25° C. The resulting mixture was stirred at 25° C. for 1.5 h.Water (75 ml) was added, pH was adjusted to 6 by adding 1N HCl.Extracted the product with ethyl acetate (75 ml). Layers were separated,organic layer was washed with brine (20 ml) and dried over anhydrousNa₂SO₄. The organic layer was filtered and concentrated in vacuo to give16.5 g of crude compound. This residue was purified by combiflash(R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f) column withgradient elution (0 to 4%) of ethyl acetate in petroleum ether to affordthe title compound (7 g, 70.5%) as an off-white solid. ¹H NMR (400 MHz,DMSO-d₆) δ 10.22 (s, 1H), 8.46 (s, 2H).

2-Amino-6-chloro-4-iodobenzaldehyde

The title compound was prepared by following an analogous reactionprotocol as described in the preparation of2-amino-4-bromo-6-fluorobenzaldehyde. ¹H NMR (400 MHz, DMSO-d₆) δ 10.26(s, 1H), 7.80-7.55 (m, 2H), 7.23 (d, J=1.4 Hz, 1H), 6.99 (d, J=1.5 Hz,1H).

1-Fluoro-2-iodo-5-methyl-4-nitrobenzene

To a stirred solution of 2-fluoro-4-methyl-5-nitroaniline (2.0 g, 11.75mmol) in conc.HC (6.15 ml, 73.8 mmol) was added a solution of sodiumnitrite (0.884 g, 12.81 mmol) in water (4 ml) in a dropwise manner at 0°C. After stirring for 15 mins, the mixture was filtered through a cottonpad and slowly poured into a stirred solution of potassium iodide (6.83g, 41.1 mmol) in water (25 ml) at 0° C. The resulting mixture wasstirred at 25° C. for 16 h. The reaction mixture was diluted with ethylacetate (20 ml) and washed with 10% aq.NaOH (50 ml), aq.sat.NaHCO₃ (50ml) successively. Layers were separated, organic layer was washed withbrine (50 ml) and was dried over anhydrous Na₂SO₄. The organic layer wasfiltered and concentrated in vacuo to give 3.1 g of crude compound. Thisresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with petroleum ether as a eluent to affordthe title compound (1.7 g, 51.5%) of the title compound as an off-whitesolid. ¹H NMR (400 MHz, Chloroform-d) δ 8.45 (d, J=5.7 Hz, 1H), 7.06 (d,1H), 2.62 (d, J=0.7 Hz, 3H); GCMS m/z=281.03 (M+, 50%).

1-(Bromomethyl)-5-fluoro-4-iodo-2-nitrobenzene

The title compound was prepared by following an analogous reactionprotocol as described in the preparation of2-(bromomethyl)-1-chloro-5-iodo-3-nitrobenzene. ¹H NMR (400 MHz,Chloroform-d) δ 8.53 (d, J=5.6 Hz, 1H), 7.31 (d, J=7.8 Hz, 1H), 4.80 (s,2H).

5-Fluoro-4-iodo-2-nitrobenzaldehyde

The title compound was prepared by following an analogous reactionprotocol as described in the preparation of2-chloro-4-iodo-6-nitrobenzaldehyde. ¹H NMR (400 MHz, Chloroform-d) δ10.42 (d, J=2.3 Hz, 1H), 8.62 (d, J=5.1 Hz, 1H), 7.60 (d, J=7.2 Hz, 1H).

2-Amino-5-fluoro-4-iodobenzaldehyde

The title compound was prepared by following an analogous reactionprotocol as described in the preparation of2-amino-4-bromo-6-fluorobenzaldehyde. ¹H NMR (400 MHz, Chloroform-d) δ9.78 (d, J=0.6 Hz, 1H), 7.17-7.13 (m, 2H), 5.98 (s, 2H).

7-Bromo-3-cyclopropylquinoline

To a stirred mixture of 2-amino-4-bromobenzaldehyde (2 g, 10.00 mmol)and 2-cyclopropylacetaldehyde (0.841 g, 10.00 mmol) in absolute ethanol(12 ml) was added a solution of KOH (0.191 g, 3.40 mmol) in ethanol (12ml) in a dropwise manner under N₂ atmosphere. The resulting mixture wasstirred at 95° C. for 5 h. The volatiles were evaporated in vacuo andthe residue was dissolved in dichloromethane (60 ml) and washed withwater (40 ml). Layers were separated, organic layer was washed withbrine (50 ml) and dried over anhydrous Na₂SO₄. The organic layer wasfiltered and concentrated in vacuo to give 2.5 g of crude compound. Thisresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution (0 to 6%) of ethylacetate in petroleum ether to afford 7-bromo-3-cyclopropylquinoline (1g, 40.3%) as a pale yellow solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.80 (d,J=2.3 Hz, 1H), 8.17 (d, J=2.1 Hz, 1H), 8.00 (d, J=2.4 Hz, 1H), 7.89-7.80(m, 1H), 7.70 (dd, J=8.8, 2.1 Hz, 1H), 2.15 (tt, J=8.1, 5.1 Hz, 1H),1.14-1.03 (m, 2H), 0.95-0.81 (m, 2H); LCMS m/z=247.83, 249.83 (M+, M+2,100%).

7-Bromo-3-(1,1-difluoroethyl)quinoline

A mixture of 1-(7-bromoquinolin-3-yl)ethan-1-one (synthesized byfollowing same reaction protocol as described in Alam, Muzaffar et al,US20120230951 A1; 2.4 g, 9.60 mmol) in diethylaminosulfur trifluoride(2.5 ml, 18.92 mmol) was stirred at 70° C. for 16 h. The resultingmixture was slowly poured into aq. sat. sodium bicarbonate (50 ml) andextracted with dichloromethane (50 ml). Layers were separated, organiclayer was washed with brine (20 ml) and dried over anhydrous Na₂SO₄. Theorganic layer was filtered and concentrated in vacuo to give 3.2 g ofcrude compound. This residue was purified by combiflash (R_(f)200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0 to 30%) of ethyl acetate in petroleum ether to afford thetitle compound (1.7 g, 65.1%) as a pale yellow solid. ¹H NMR (400 MHz,DMSO-d₆) δ 9.13 (d, J=2.4 Hz, 1H), 8.71 (s, 1H), 8.34 (d, J=2.1 Hz, 1H),8.11 (d, J=8.7 Hz, 1H), 7.88 (dd, J=8.7, 2.0 Hz, 1H), 2.14 (t, J=19.2Hz, 3H), LCMS m/z=271.90, 273.90 (M+1; 100%).

7-Bromo-3-chloro-8-fluoroquinoline

To a stirred solution of 7-bromo-8-fluoroquinoline (synthesized byfollowing same reaction protocol as described in Ghergurovich, JonathanMichael et al, WO2013028447 A1, 3.4 g, 15.04 mmol) in DMF (10 ml) wasadded N-chlorosuccinimide (4.02 g, 30.1 mmol) at 25° C. The reactionmixture was stirred at 100° C. for 16 h. The reaction mixture was cooledto 25° C. and poured onto ice cold water (100 ml) and stirred for 30minutes. The precipitate was collected by filtration and washed withwater. The precipitate was dried in vacuo to afford the title compound(2 g, 51%) as an off-white solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.90(d, J=2.3 Hz, 1H), 8.18 (t, J=1.9 Hz, 1H), 7.72 (dd, J=8.9, 6.1 Hz, 1H),7.48 (dd, J=8.8, 1.5 Hz, 1H); LCMS m/z=261.71 (M+; 100%).

7-Bromo-3-chloro-5-fluoroquinoline

To a stirred solution of 2-amino-4-bromo-6-fluorobenzaldehyde (3.36 g,15.41 mmol) in toluene (35 ml) was added 2-chloro-1,1-dimethoxyethane(2.304 g, 18.49 mmol) followed by p-toluene sulfonic acid monohydrate(2.93 g, 15.41 mmol) at 25° C. The resulting mixture was stirred at 110°C. using Dean Stark apparatus for 4 h under N₂ atmosphere. The reactionmixture was diluted with ethyl acetate (100 ml) and basified withaq.sat.NaHCO₃ (75 ml). Layers were separated, organic layer was washedwith brine (20 ml) and dried over anhydrous Na₂SO₄. The organic layerwas filtered and concentrated in vacuo to give 1.1 g of crude compound.This residue was purified by combiflash (R_(f)200, Teledyne/Isco)instrument onto a Redisep® R_(f) column with gradient elution (0 to 2%)of ethyl acetate in petroleum ether to afford the title compound (1.64g, 40.9%) as a light green solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.88(d, J=2.4 Hz, 1H), 8.38 (d, J=2.4 Hz, 1H), 8.15 (s, 1H), 7.45 (ddd,J=9.0, 3.5, 1.8 Hz, 1H); LCMS m/z=261.76 (M+1, 100%).

Intermediates in table-1 were synthesized by following an analogousreaction protocol as was used for the preparation of7-bromo-3-chloro-5-fluoroquinoline using the appropriate startingmaterials.

TABLE 1 Starting materials Intermediate’s Structure used ¹H NMR and LCMSdata

2-Amino-4-bromo- 5- fluorobenzaldehyde, which was synthesized as perUS2014/200216 A1 ¹H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 1H), 8.43 −8.38 (m, 1H), 8.12 − 8.08 (m, 1H), 7.47 (d, J = 8.4 Hz, 1H); LCMS m/z =261.83 (M + 1; 100%).

2-Amino-6-chloro- 4-iodobenzaldehyde ¹H NMR (400 MHz, Chloroform-d) δ8.85 (d, J = 2.3 Hz, 1H), 8.50 (dd, J = 2.3, 0.9 Hz, 1H), 8.48 − 8.45(m, 1H), 7.96 (d, J = 1.6 Hz, 1H).

2-Amino-4-bromo- 6- fluorobenzaldehyde Crude was taken as such for thenext step

2-Amino-5-fluoro-4- iodobenzaldehyde ¹H NMR (400 MHz, Chloroform-d) δ8.88 (d, J = 2.2 Hz, 1H), 8.61 (d, J = 6.0 Hz, 1H), 8.27 (d, J = 2.3 Hz,1H), 7.39 (d, J = 7.8 Hz, 1H); LCMS m/z = 351.03, 353.03 (M-1, M + 1,60%).

7-Bromo-3-chloro-5-fluoroquinoline 1-oxide

A mixture of 7-bromo-3-chloro-5-fluoroquinoline (1.64 g, 6.30 mmol) andm-CPBA (2.90 g, 12.59 mmol) in CHCl₃ (30 ml) was heated at 50° C. for 16h. The reaction mixture was diluted with chloroform (50 ml) and washedwith aq.sat. Na₂SO₃ (50 ml) followed by aq.sat.NaHCO₃ (50 ml). Layerswere separated, organic layer was washed with brine (50 ml) and driedover anhydrous Na₂SO₄. The organic layer was filtered and concentratedin vacuo to give 1.35 g of crude compound. This residue was purified bycombiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0 to 20%) of ethyl acetate in petroleumether to afford the title compound (542 mg, 31.1%) as a light brownsolid. ¹H NMR (400 MHz, DMSO-d₆) δ 8.97 (d, J=1.8 Hz, 1H), 8.46 (s, 1H),8.17-8.10 (m, 1H), 8.03 (dd, J=9.5, 1.9 Hz, 1H); LCMS m/z=275.83, 277.83(M+, M+2; 100%).

Intermediates in table-2 were synthesized by following an analogousreaction protocol as was used for the preparation of7-bromo-3-chloro-5-fluoroquinoline 1-oxide using the appropriatestarting materials.

TABLE 2 Intermediate's Structure Starting materials used ¹H NMR and LCMSdata

7-Bromo-3- methylquinoline ¹H NMR (400 MHz, DMSO- d6) δ 8.60 (dd, J =12.2, 1.7 Hz, 2H), 7.97 (d, J = 8.7 Hz, 1H), 7.85 (dd, J = 8.7, 2.0 Hz,1H), 7.77 (q, J = 1.1 Hz, 1H), 2.40 (d, J = 1.0 Hz, 3H); LCMS m/z =237.9, 239.9 (M+, M + 2, 100%).

7-Bromo-3- cyclopropylquinoline ¹H NMR (400 MHz, DMSO- d6) δ 8.58 (dd, J= 13.9, 1.7 Hz, 2H), 7.93 (d, J = 8.7 Hz, 1H), 7.84 (dd, J = 8.7, 2.1Hz,1H), 7.66 (s, 1H), 2.08 (tt, J = 8.4, 5.0 Hz, 1H), 1.12-1.04 (m, 2H),0.95-0.87 (m, 2H); LCMS m/z = 263.83, 265.83 (M+, M + 2, 100%).

7-Bromo-3-(1,1- difluoroethyl) quinoline LCMS m/z = 289.96 (M + 1; 100%)

7-Bromo-3-methoxy quinoline, which was synthesized as per Adams,Nicholas David et al, WO2014/008223 A1. Crude was taken as such for thenext step

7-Bromo-3-chloro-6- fluoroquinoline ¹H NMR (400 MHz, DMSO- d6) δ 8.87(d, J = 1.8 Hz, 1H), 8.75 (d, J = 6.6 Hz, 1H), 8.14- 8.03 (m, 2H); LCMSm/z = 275.77 (M + 1; 60%).

7-Bromo-3-chloro-8- fluoroquinoline ¹H NMR (400 MHz, DMSO- d6) δ 8.78(d, J = 1.5 Hz, 1H), 8.17 (s, 1H), 7.99 (dd, J = 8.8, 5.7 Hz, 1H), 7.80(dd, J = 8.8, 1.6 Hz, 1H); LCMS m/z = 277.83 (M + 1; 100%).

3,5-Dichloro-7- iodoquinoline ¹H NMR (400 MHz, DMSO- d6) δ 8.95 (d, J =1.7 Hz, 1H), 8.80 (t, J = 1.3 Hz, 1H), 8.33 (d, J = 1.6 Hz, 1H), 8.08(t, J = 1.3 Hz, 1H).

3,7-Dibromo-5- fluoroquinoline LCMS m/z = 322.0 (M + 1; 100%)

3-Bromo-6-fluoro-7- iodoquinoline ¹H NMR (400 MHz, DMSO- d6) δ 8.91 (d,J = 6.0 Hz, 1H), 8.87 (d, J = 1.5 Hz, 1H), 8.22 (t, J = 1.1 Hz, 1H).7.92 (d, J = 8.3 Hz, 1H).

7-Bromo-2,3-dichloro-5-fluoroquinoline

To a stirred solution of 7-bromo-3-chloro-5-fluoroquinoline 1-oxide (542mg, 1.960 mmol) in CHCl₃ (10 ml) was added POCl₃ (1.867 ml, 20.03 mmol)at 25° C. The resulting mixture was stirred at 65° C. for 2 h under N₂atmosphere. The reaction mixture was poured onto ice cold water (50 ml),carefully basified with solid NaHCO₃ and extracted the product withdichloromethane (50 ml). Layers were separated, organic layer was washedwith brine (50 ml) and was dried over anhydrous Na₂SO₄. The organiclayer was filtered and concentrated in vacuo to give 1.2 g of crudecompound. This residue was purified by combiflash (R_(f)200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0 to 10%) of ethyl acetate in petroleum ether to afford thetitle compound (410 mg, 70.9%) as a white solid. ¹H NMR (400 MHz,Chloroform-d) δ 8.49-8.43 (m, 1H), 8.04 (dt, J=1.9, 1.0 Hz, 1H), 7.45(dd, J=8.9, 1.7 Hz, 1H); LCMS m/z=296.19 (M+1; 100%). Intermediates intable-3 were synthesized by following an analogous reaction protocol aswas used for the preparation of 7-bromo-2,3-dichloro-5-fluoroquinolineusing the appropriate starting materials.

TABLE 3 Intermediate's Structure Starting materials used ¹H NMR and LCMSdata

7-Bromo-3- methylquinoline 1-oxide ¹H NMR (400 MHz. DMSO- d6) δ 8.40 (t,J = 1.0 Hz. 1H), 8.17 (d. J = 2.0 Hz, 1H), 7.94 (d, J = 8.7 Hz, 1H),7.78 (dd, J = 8.7, 2.0 Hz, 1H), 2.48 (d, J = 1.0 Hz, 3H); LCMS m/z =256, 258 (M+, M + 2, 100%).

7-Bromo-3- cyclopropylquinoline 1- oxide ¹H NMR (400 MHz, DMSO- d6) δ8.16 (d, J = 3.0 Hz, 2H), 7.92 (d, J = 8.7 Hz, 1H), 7.77 (dd, J = 8.7,2.0 Hz, 1H), 2.21 (tt, J = 8.4, 5.3 Hz, 1H), 1.10 (dt, J = 8.5, 3.2 Hz,2H), 0.92- 0.81 (m, 2H); LCMS m/z = 281.90, 283.90 (M+, M + 2, 100%).

7-Bromo-3-(1,1- difluoroethyl) quinoline 1- oxide LCMS m/z = 306, 308(M+, M + 2; 100%).

7-Bromo-3- methoxyquinoline 1-oxide LCMS m/z = 271.69, 273.69

7-Bromo-3-chloro-6- fluoroquinoline 1-oxide ¹H NMR (400 MHz,Chloroform-d) δ 8.31 (d, J = 6.3 Hz, 1H), 8.23-8.18 (m, 1H), 7.48 (d, J= 8.2 Hz, 1H).

7-Bromo-3-chloro-8- fluoroquinoline 1-oxide ¹H NMR (400 MHz, DMSO- d6) δ8.94 (d, J = 1.6 Hz, 1H), 7.97 (dd, J = 8.9, 6.3 Hz, 1H), 7.83 (dd, J =8.9, 1.3 Hz, 1H), LCMS m/z = 295.65 (M + 1; 100%).

3,5-Dichloro-7- iodoquinoline 1-oxide ¹H NMR (400 MHz, Chloroform-d) δ8.59 (d, J = 0.8 Hz, 1H), 8.38 (dd, J = 1.6, 0.8 Hz, 1H), 7.96 (d. J =1.5 Hz. 1H).

3,7-Dibromo-5- fluoroquinoline 1-oxide Crude was taken as such for thenext step

3-Bromo-6-fluoro-7- iodoquinoline 1-oxide ¹H NMR (400 MHz, Chloroform-d)δ 8.54 (dd, J = 5.9, 0.7 Hz, 1H), 8.38 (s, 1H), 7.40 (d, J = 7.6 Hz,1H).

7-Bromo-3-chloro-5-fluoroquinolin-2-amine

A mixture of 7-bromo-2,3-dichloro-5-fluoroquinoline (410 mg, 1.390mmol), aqueous ammonia (9.74 ml, 250 mmol) in dioxane (10 ml) was heatedat 120° C. in a steel bomb for 24 h. The reaction mixture was dilutedwith ethyl acetate (20 ml) and washed with water (20 ml). Layers wereseparated, organic layer was washed with brine (20 ml) and dried overanhydrous Na₂SO₄. The organic layer was filtered and concentrated invacuo to give 1.15 g of crude compound. This residue was purified bycombiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0 to 30%) of ethyl acetate in petroleumether to afford the title compound (297 mg, 78%) as a white solid. ¹HNMR (400 MHz, DMSO-d₆) 8.23 (s, 1H), 7.51 (d, J=1.9 Hz, 1H), 7.32 (dd,J=9.5, 1.9 Hz, 1H), 7.256 (s, 2H); LCMS m/z=276.83 (M+1; 100%).

Intermediates in table-4 were synthesized by following an analogousreaction protocol as was used for the preparation of7-bromo-3-chloro-5-fluoroquinolin-2-amine using the appropriate startingmaterials.

TABLE 4 Intermediate's Structure Starting materials used ¹H NMR and LCMSdata

7-Bromo-2-chloro-8- fluoroquinoline ¹H NMR (400 MHz, DMSO-d6) δ 7.95(dd, J = 8.9, 1.8 Hz, 1H), 7.42 (dd, J = 8.7, 1.4 Hz, 1H), 7.35- 7.27(m, 1H), 6.93 (s, 2H), 6.88- 6.79 (m, 1H); LCMS m/z = 240.8 (M+; 100%)

7-Bromo-2-chloro-3- methylquinoline ¹H NMR (400 MHz, DMSO-d6) δ 7.75 (t,J = 1.0 Hz, 1H), 7.60 (d, J = 2.0 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H),7.25 (dd, J = 8.5, 2.0 Hz, 1H), 6.51 (s, 2H), 2.19 (d, J = 1.1 Hz, 3H):LCMS m/z = 237, 239 (M+, M + 2, 100%).

7-Bromo-2-chloro-3- isopropyl quinoline LCMS m/z = 265.1, 267.1 (M+, M +2, 100%).

7-Bromo-2-chloro-3- cyclopropyl quinoline ¹H NMR (400 MHz, DMSO-d6) δ7.63 (s, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.55 (d, J = 8.5 Hz, 1H), 7.24(dd, J = 8.5, 2.0 Hz, 1H), 6.65 (s, 2H), 1.80 (tdd, J = 8.2, 4.6, 2.9Hz, 1H), 1.01-0.92 (m, 2H), 0.69- 0.62 (m, 2H); LCMS m/z = 262.83,264.83 (M+, M + 2, 100%).

7-Bromo-2-chloro-3- (1,1- difluoroethyl)quinoline LCMS m/z = 287.96 (M +1, 100%).

7-Bromo-2-chloro-3- methoxyquinoline LCMS m/z = 253, 255 (M+, M + 2;100%).

7-Bromo-2,3-dichloro- 6-fluoro quinoline ¹H NMR (400 MHz, DMSO-d6) δ8.23 (s, 1H), 7.79 (d, J = 6.7 Hz, 1H), 7.67 (dd, J = 9.3, 2.0 Hz, 1H),6.97 (s, 2H); LCMS m/z = 276.83 (M + 1; 100%).

7-Bromo-2,3-dichloro- 8-fluoro quinoline ¹H NMR (400 MHz, DMSO-d6) δ8.32 (d, J = 1.7 Hz, 1H), 7.30 (s, 2H), 7.35-7.16 (m, 2H), LCMS m/z =276.86 (M + 1; 100%).

2,3,5-Trichloro-7- iodoquinoline ¹H NMR (400 MHz, DMSO-d6) δ 8.22 (s,1H), 7.94-7.81 (m, 1H), 7.67 (d, J = 1.6 Hz, 1H), 7.24 (s, 2H).

3,7-Dibromo-2-chloro- 5-fluoro quinoline ¹H NMR (400 MHz, DMSO-d6) δ8.39 (d, J = 0.7 Hz, 1H), 7.50 (d, J = 1.7 Hz, 1H), 7.31 (dd, J = 9.5,1.8 Hz, 1H), 7.14 (s, 2H); LCMS m/z = 318.96, 320.34. 322.34 (M − 1, M+,M + 2; 100%).

3-Bromo-2-chloro-6- fluoro-7-iodoquinoline ¹H NMR (400 MHz, DMSO-d6) δ8.39 (s, 1H), 7.97 (d, J = 5.9 Hz, 1H), 7.55 (d, J = 8.5 Hz, 1H), 6.82(s, 2H).

7-Bromo-3-chloro-5-fluoro-N-(4-methoxybenzyl)quinolin-2-amine

The title compound was prepared by following an analogous reactionprotocol as described in Banka, Anna Lindsey et al, WO2012/037108 A1using appropriate starting materials. ¹H NMR (400 MHz, DMSO-d6) δ 8.22(d, J=0.8 Hz, 1H), 7.96 (t, J=6.1 Hz, 1H), 7.58 (dd, J=1.8, 1.0 Hz, 1H),7.39-7.28 (m, 3H), 6.91-6.82 (m, 2H), 4.62 (d, J=6.1 Hz, 2H), 3.71 (s,3H); LCMS m/z=397 (M+1; 100%).

A mixture of 3,7-dibromo-5-fluoroquinolin-2-amine (2.05 g, 6.41 mmol),Et₃N (2.68 ml, 19.22 mmol), DMAP (0.078 g, 0.641 mmol) and Boc anhydride(3.12 ml, 13.45 mmol) in THF (25 ml) was stirred at 25° C. for 16 h. Thereaction mixture was diluted with ethyl acetate (20 ml) and washed withwater (20 ml). Layers were separated, organic layer was washed withbrine (20 ml) and dried over anhydrous Na₂SO₄. The organic layer wasfiltered and concentrated in vacuo to give 3.9 g of crude compound. Thisresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution (0 to 5%) of ethylacetate in petroleum ether to afford the di-boc compound (2.5 g, 75%) asan off-white solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.65 (d, J=0.8 Hz,1H), 8.08 (q, J=1.2 Hz, 1H), 7.46 (dd, J=8.9, 1.7 Hz, 1H), 1.42 (s,18H).

2-Amino-7-bromoquinoline-3-carbonitrile

A mixture of 2-amino-4-bromobenzaldehyde (0.448 g, 2.240 mmol),malononitrile (0.222 g, 3.36 mmol) and piperidine (0.111 ml, 1.120 mmol)in ethanol (10 ml) was stirred at 100° C. for 16 h. The volatiles wereevaporated in vacuo and the residue was purified by combiflash(R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f) column withgradient elution (0 to 10%) of ethyl acetate in petroleum ether toafford the title compound (0.343 g, 61.7%) as an off-white solid. ¹H NMR(400 MHz, DMSO-d6) δ 8.71 (s, 1H), 7.74-7.65 (m, 2H), 7.42 (dd, J=8.6,2.0 Hz, 1H), 7.20 (s, 2H); LCMS m/z=248, 250 (M+, M+2, 100%).

7-Bromo-N-(4-methoxybenzyl)quinazolin-2-amine

The title compound was prepared by following an analogous reactionprotocol as described in Li, Liansheng et al, WO2017/087528 A1; LCMSm/z=344.1 (M+, 100%).

7-Bromo-3-fluoroquinolin-2-amine

The title compound was prepared by an following analogous reactionprotocol as described in Banka, Anna Lindsey et al, WO2012/037108 A1.

7-Bromo-3-chloroquinolin-2-amine

The title compound was prepared by following an analogous reactionprotocol as described in Banka, Anna Lindsey et al, WO2012/037108 A1.

7-Bromo-3-chloro-N-(4-methoxybenzyl)quinolin-2-amine

The title compound was prepared by following an analogous reactionprotocol as described in Banka, Anna Lindsey et al, WO2012/037108 A1.

7-Bromo-3-chloro-N,N-bis(4-methoxybenzyl)quinolin-2-amine

To a stirred suspension of 7-bromo-3-chloroquinolin-2-amine (2.0 g, 7.77mmol) in DMF (20 ml) was added NaH (0.932 g, 23.30 mmol) at 0° C. Theresulting mixture was stirred at 0° C. for 15 min. Then1-(chloromethyl)-4-methoxybenzene (3.65 g, 23.30 mmol) was addeddropwise under N₂ atmosphere. The reaction mixture was then stirred for16 h at 25° C. The reaction mixture was poured into ice water (150 mL)and extracted with ethyl acetate (150 ml). Layers were separated,organic layer was washed with brine (100 ml) and dried over anhydrousNa₂SO₄. The organic layer was filtered and concentrated in vacuo to give3.87 g of crude compound. This residue was purified by combiflash(R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f) column withgradient elution (0 to 30%) of ethyl acetate in petroleum ether toafford the title compound (2.2 g, 56.9%) as an off-white solid. 1H NMR(400 MHz, DMSO-d6) δ 8.45 (s, 1H), 7.89 (d, J=1.9 Hz, 1H), 7.77 (d,J=8.6 Hz, 1H), 7.56 (dd, J=8.6, 2.0 Hz, 1H), 7.31-7.22 (m, 4H),6.93-6.82 (m, 4H), 4.54 (s, 4H), 3.70 (s, 6H); LCMS m/z=498.97 (M+1;100%).

3-Bromo-7-iodo-N-(4-methoxybenzyl)quinolin-2-amine

The title compound was prepared by following an analogous reactionprotocol as described in Banka, Anna Lindsey et al, WO2012/037108 A1.

6-Bromo-3,3-dimethylindoline-2-thione

The suspension of 6-bromo-3,3-dimethylindolin-2-one (3.5 g, 14.58 mmol),which was synthesized by following an analogous reaction protocol as wasreported in WO2015/177110, A1 and Lawesson's reagent (7.66 g, 18.95mmol) in toluene (15 ml) was heated at 100° C. for 3 h under N₂atmosphere. Solvent was evaporated in vacuo and this residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0-20%) of ethyl acetate inpetroleum ether to afford the title compound (3.3 g, 88%) as anoff-white solid. ¹H NMR (400 MHz, DMSO-d6) δ 12.67 (s, 1H), 7.40 (d,J=7.9 Hz, 1H), 7.31 (dd, J=7.9, 1.8 Hz, 1H), 7.15 (d, J=1.7 Hz, 1H),1.30 (s, 6H); LCMS m/z=256.89 (M+1; 30%).

6-Bromo-3,3-dimethyl-2-(methylthio)-3H-indole

To a stirred suspension of 6-bromo-3,3-dimethylindoline-2-thione (3 g,11.71 mmol) in THF (40 ml) was added NaH (0.703 g, 17.57 mmol) at 0° C.The resulting mixture was stirred for 15 min at 0° C. Methyl iodide(1.098 ml, 17.57 mmol) was added and stirred the reaction mixture for 1h at 0° C. under N₂ atmosphere. The reaction mixture was diluted withethyl acetate (50 ml) and washed with water (50 ml). Layers wereseparated, organic layer was washed with brine (50 ml) and dried overanhydrous sodium sulphate. The organic layer was filtered andconcentrated in vacuo to give 3.5 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0-5%) of ethyl acetate inpetroleum ether to afford the title compound (3.1 g, 98%) as a whitesolid. ¹H NMR (400 MHz, DMSO-d6) δ 7.60 (d, J=1.7 Hz, 1H), 7.41 (d,J=7.9 Hz, 1H), 7.32 (dd, J=7.9, 1.8 Hz, 1H), 2.60 (s, 3H), 1.29 (s, 6H);LCMS m/z=269.90 (M+; 40%).

6′-Bromospiro[cyclobutane-1,3′-indoline]-2′-thione

The title compound was prepared by following an analogous reactionprotocol as was described in the preparation of6-bromo-3,3-dimethylindoline-2-thione. LCMS m/z=267.65 (M+; 20%).

6′-Bromo-2′-(methylthio)spiro[cyclobutane-1,3′-indole]

The title compound was prepared by following an analogous reactionprotocol as was described in the preparation of6-bromo-3,3-dimethyl-2-(methylthio)-3H-indole. ¹H NMR (400 MHz,Chloroform-d) δ 7.63 (d, J=1.7 Hz, 1H), 7.44 (d, J=7.9 Hz, 1H), 7.32(dd, J=7.9, 1.7 Hz, 1H), 2.73 (s, 3H), 2.61-2.46 (m, 4H), 2.37-2.30 (m,2H); LCMS m/z=281.78, 283.78 (M+, M+2; 100%).

6′-Bromospiro[cyclobutane-1,3′-indol]-2′-amine

To stirred solution of6′-bromo-2′-(methylthio)spiro[cyclobutane-1,3′-indole] (1.2 g, 4.25mmol) in 7N ammonia in methanol (15 ml, 371 mmol) was heated at 100° C.for 16 h. Solvent was evaporated in vacuo and this residue was purifiedby combiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0-10%) of methanol in dichloromethane toafford the title compound (650 mg, 60.9%) as white solid. ¹H NMR (400MHz, DMSO-d6) δ 7.69 (s, 2H), 7.46 (d, J=8.2 Hz, 1H), 7.01 (h, J=1.8 Hz,2H), 2.63-2.53 (m, 2H), 2.43-2.30 (m, 1H), 2.23-2.09 (m, 3H); LCMSm/z=250.87 (M+; 100%).

7-Bromo-3-methylimidazo[1,2-a]pyridine

The title compound was prepared by following an analogous reactionprotocol as was described in Dubois., Laurent et al, WO 2009/112679 A1.

2-(Methylamino)quinolin-7-ol

The title compound was prepared by following an analogous reactionprotocol as was described in Doherty, Elizabeth M. et. al, Journal ofMedicinal Chemistry, 2007, vol. 50, #15, p. 3515-3527.

3-Bromo-N-(4-methoxybenzyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

A mixture of 3-bromo-7-iodo-N-(4-methoxybenzyl)quinolin-2-amine (1.5 g,3.20 mmol), bispinacolotodiboron (0.974 g, 3.84 mmol),[1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II), complexwith dichloromethane (0.261 g, 0.320 mmol) and potassium acetate (0.533g, 5.44 mmol)) in DMSO (50 ml) was heated at 80° C. for 15 min in apreheated oil bath. The reaction mixture was allowed to cool to 25° C.,diluted with ethyl acetate (50 ml) and poured onto ice-cold water (100ml). Layers were separated, organic layer was washed with brine (50 ml)and dried over anhydrous sodium sulphate. The organic layer was filteredand concentrated in vacuo to give 2.5 g of crude compound. This residuewas purified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0-7%) of ethyl acetate inpetroleum ether to afford the title compound (1.35 g, 90%) as anoff-white solid. ¹H NMR (400 MHz, DMSO-d₆) δ 8.42 (d, J=0.7 Hz, 1H),7.86 (d, J=1.1 Hz, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.43 (dd, J=7.9, 1.1 Hz,1H), 7.40-7.32 (m, 3H), 6.99-6.74 (m, 2H), 4.62 (d, J=6.0 Hz, 2H), 3.71(s, 3H), 1.32 (s, 12H); LCMS m/z=468.89 (M+; 100%).

3-Bromo-2-((4-methoxybenzyl)amino)quinolin-7-ol

To a stirred solution of3-bromo-N-(4-methoxybenzyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine(0.35 g, 0.746 mmol) in THF (20 ml) was added AcOH (0.064 ml, 1.119mmol) dropwise at 0° C. and stirred for 1 h. Aq. H₂O₂ (0.5 ml, 1.492mmol) was added slowly at 0° C. The resulting mixture was stirred at 25°C. for 5 h. The reaction mixture was diluted with ethyl acetate (20 ml)and washed with aq.sat.Na₂SO₃ (20 ml). Layers were separated, organiclayer was washed with brine (20 ml) and dried over anhydrous sodiumsulphate. The organic layer was filtered and concentrated in vacuo togive 0.41 g of crude compound. This residue was purified by combiflash(R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f) column withgradient elution (0-25%) of ethyl acetate in petroleum ether to affordthe title compound (0.13 g, 48.5%) as an off-white solid. LCMSm/z=359.22 (M+; 100%).

3-Chloro-5-fluoro-N-(4-methoxybenzyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of3-bromo-N-(4-methoxybenzyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine.¹H NMR (400 MHz, Chloroform-d) 61H NMR (400 MHz, Chloroform-d) δ 8.17(d, J=0.9 Hz, 1H), 8.07 (s, 1H), 7.41-7.36 (m, 2H), 7.29 (dd, J=10.0,0.8 Hz, 1H), 6.94-6.89 (m, 2H), 5.69 (s, 1H), 4.77 (d, J=5.4 Hz, 2H),3.83 (s, 3H), 1.29 (s, 12H); LCMS m/z=443.05 (M+; 100%).

3-Chloro-5-fluoro-2-((4-methoxybenzyl)amino)quinolin-7-ol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of3-bromo-2-((4-methoxybenzyl)amino)quinolin-7-ol. ¹H NMR (400 MHz,DMSO-d6) δ 10.19 (d, J=1.0 Hz, 1H), 8.02 (s, 1H), 7.55 (t, J=6.2 Hz,1H), 7.43-7.28 (m, 2H), 6.91-6.82 (m, 2H), 6.67 (d, J=2.1 Hz, 1H), 6.57(dd, J=11.7, 2.2 Hz, 1H), 4.60 (d, J=6.0 Hz, 2H), 3.71 (s, 3H); LCMSm/z=333.15, 335.15 (M+, M+2; 30%).

N2-(4-Methoxybenzyl)quinoline-2,7-diamine

A mixture of 7-bromo-N-(4-methoxybenzyl)quinolin-2-amine (0.6 g, 1.748mmol) copper(I) iodide (0.033 g, 0.175 mmol), andN1,N1-dimethylethane-1,2-diamine (0.171 ml, 1.748 mmol) in AMMONIA(0.757 ml, 35.0 mmol) and DMSO (1 ml) at 130° C. for 15 h.

The resulting suspension was cooled to 25° C. and saturated aqueoussodium sulphate solution (5 mL) was added. The resulting mixture wasextracted with ethyl acetate (20 ml×3). The organic layer was separated,dried over MgSO4, filtered and concentrated. This residue was purifiedby combiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0-5%) of methanol in dichloromethane toafford the title compound (0.18 g, 36.9%) as a brown solid. ¹H NMR (400MHz, DMSO-d6) δ 7.55 (d, J=8.7 Hz, 1H), 7.34-7.29 (m, 2H), 7.25 (d,J=8.4 Hz, 1H), 7.07 (t, J=5.8 Hz, 1H), 6.91-6.83 (m, 2H), 6.56 (d, J=2.2Hz, 1H), 6.52 (dd, J=8.4, 2.2 Hz, 1H), 6.40 (d, J=8.7 Hz, 1H), 5.32 (s,2H), 4.49 (d, J=5.8 Hz, 2H), 3.72 (s, 3H); LCMS m/z=280.2 (M+1, 100%).

N2-(4-Methoxybenzyl)-N7-methylquinoline-2,7-diamine

A mixture of 7-bromo-N-(4-methoxybenzyl)quinolin-2-amine (0.5 g, 1.457mmol), methanamine (7.54 ml, 7.28 mmol) and copper (0.046 g, 0.728 mmol)was stirred at 110° C. in a sealed tube for 12 h. The reaction mixturewas diluted with ethyl acetate (20 ml) and washed with water (20 ml).The organic layer was separated, dried over MgSO₄, filtered andconcentrated. This residue was purified by combiflash (R_(f)200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0-5%) of methanol in dichloromethane to afford the titlecompound (0.4 g, 94%) as a brown liquid. LCMS m/z=294.09 (M+1; 100%).

S-(2-((4-Methoxybenzyl)amino)quinolin-7-yl) ethanethioate

To a stirred solution of 7-bromo-N-4-methoxybenzyl)quinolin-2-amine (2g, 5.83 mmol), potassium thioacetate (1.331 g, 11.65 mmol), DIEA (2.035ml, 11.65 mmol) and xantphos (0.337 g, 0.583 mmol) in 1,4-dioxane (20ml) was added Pd₂(dba)₃ (0.534 g, 0.583 mmol) at 25° C. under N₂atmosphere. The resulting mixture was stirred at 110° C. for 1.5 h undermicrowave condition. The reaction mixture was diluted with ethyl acetate(20 ml) and washed with water (20 ml). The organic layer was separated,dried over MgSO₄, filtered and concentrated. This residue was purifiedby combiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0-20%) of ethyl acetate in petroleum etherto afford the title compound (0.67 g, 34%) as an off-white solid. ¹H NMR(400 MHz, Chloroform-d) δ 7.87-7.80 (m, 2H), 7.63 (d, J=8.3 Hz, 1H),7.39-7.32 (m, 2H), 7.28-7.23 (m, 1H), 6.95-6.87 (m, 2H), 6.67 (d, J=9.0Hz, 1H), 5.21 (s, 1H), 4.67 (d, J=5.4 Hz, 2H), 3.82 (s, 3H), 2.47 (s,3H); LCMS m/z=339.22 (M+1; 100%).

2-((4-Methoxybenzyl)amino)quinoline-7-thiol

To a stirred solution of S-(2-((4-methoxybenzyl)amino)quinolin-7-yl)ethanethioate (0.67 g, 1.98 mmol) in 20 mL of ethanol was added KOH(0.33 g, 5.94 mmol) at 25° C. The resulting mixture was stirred at 25°C. for 1 h. The reaction mixture was quenched with sat.aqueous NH₄Cl (20ml) and extracted with ethyl acetate (20 ml). The organic layer wasseparated, dried over MgSO4, filtered and concentrated in vacuo to givethe title compound (0.56 g, 95%) as a brown solid. ¹H NMR (400 MHz,Chloroform-d) δ 7.77 (d, J=8.9 Hz, 1H), 7.64 (d, J=1.8 Hz, 1H), 7.46 (d,J=8.3 Hz, 1H), 7.37-7.32 (m, 2H), 7.10 (dd, J=8.3, 1.9 Hz, 1H),6.93-6.87 (m, 2H), 6.58 (d, J=8.9 Hz, 1H), 5.58 (s, 1H), 4.64 (d, J=5.3Hz, 2H), 3.82 (s, 3H); LCMS m/z=297.09 (M+; 100%).

S-(2-(Bis(4-methoxybenzyl)amino)-3-chloroquinolin-7-yl) ethanethioate

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation ofS-(2-((4-methoxybenzyl)amino)quinolin-7-yl) ethanethioate. LCMSm/z=493.30 (M+; 100%).

2-(Bis(4-methoxybenzyl)amino)-3-chloroquinoline-7-thiol

To a solution of solution ofS-(2-(bis(4-methoxybenzyl)amino)-3-chloroquinolin-7-yl) ethanethioate(300 mg, 0.608 mmol) in ethanol (9 ml) was added KOH (51.2 mg, 0.913mmol) at 25° C. The mixture was heated at 50° C. for 2 h. The reactionsolution was allowed to cool to 25° C., adjusted pH to 4 with HCl (1N)and concentrated in vacuo to get 0.4 g of crude compound, which wastriturated with diethyl ether (20 ml) to get the title compound (200 mg,72.9%) as an off-white solid. LCMS m/z=450.42 (M+; 100%).

((3aR,6R,6aS)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

The title compound was prepared by following the same reaction protocolas was described in Kenneth A. Jacobson et. al; Purinergic Signalling(2015) 11:371-387.((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methyl4-methylbenzenesulfonate

To a stirred solution of((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methanol(0.5 g, 1.554 mmol) in dichloromethane (10 ml) was added TEA (0.651 ml,4.66 mmol), DMAP (0.038 g, 0.311 mmol), followed by a slow addition ofp-TsCl (0.355 g, 1.865 mmol) at 0° C. and stirred for 10 mins. Theresulting mixture was stirred at 25° C. for 2 h. The reaction mixturewas diluted with ethyl acetate (20 ml) and washed with water (20 ml).The organic layer was separated, dried over MgSO₄, filtered andconcentrated in vacuo to give 0.71 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0-10%) of ethyl acetate inpetroleum ether to afford the title compound (0.282 g, 38.1%) as a paleyellow liquid. ¹H NMR (400 MHz, Chloroform-d) δ 8.69 (t, J=2.8 Hz, 1H),7.89-7.81 (m, 2H), 7.42-7.34 (m, 2H), 7.12 (s, 1H), 6.64 (d, J=3.8 Hz,1H), 5.86 (d, J=12.4 Hz, 2H), 5.36 (d, J=5.6 Hz, 1H), 4.90-4.77 (m, 2H),4.63 (t, J=4.5 Hz, 1H), 2.52-2.45 (m, 3H), 1.45 (s, 3H), 1.34 (s, 3H);LCMS m/z=476.17 (M+; 100%).

(3aS,4R,6aR)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde

To a stirred solution of((3aS,4R,6aR)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methanol(2.50 g, 7.77 mmol) in CH₂Cl₂ (40 ml) at 0° C., was added Dess-MartinPeriodinane (3.95 g, 9.32 mmol) portion-wise and stirred for 1 h. Thereaction mixture was diluted with dichloromethane (50 ml) and washedwith water (50 ml). The organic layer was separated, dried over MgSO₄,filtered and concentrated in vacuo to give 2.71 g of crude compound.This residue was purified by combiflash (R_(f)200, Teledyne/Isco)instrument onto a Redisep® R_(f) column with gradient elution (0-30%) ofethyl acetate in petroleum ether to afford the title compound (2.32 g,93%) as a colorless oil. ¹H NMR (400 MHz, Chloroform-d) δ 10.00 (s, 1H),8.67 (s, 1H), 7.12 (d, J=3.6 Hz, 1H), 6.78 (dd, J=2.6, 0.9 Hz, 1H), 6.69(d, J=3.7 Hz, 1H), 5.97 (dt, J=2.8, 1.4 Hz, 1H), 5.76 (dd, J=5.9, 1.5Hz, 1H), 4.88 (dt, J=5.9, 1.1 Hz, 1H), 1.54 (s, 3H), 1.40 (s, 3H); LCMSm/z=320.2 (M+1, 100%).

4-Chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

To a cooled suspension of methyl(triphenyl)phosphonium bromide (5.03 g,14.07 mmol) in THF (30 mL) at 0° C., was added 1M KHMDS in THF (14.07mL, 14.07 mmol) slowly and stirred for 5 min. The reaction mixture wasallowed to warm to 25° C. and stirred for 10 min. Cooled the reactionmixture to 0° C. and slowly added a solution of(3aS,4R,6aR)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde (1.8 g, 5.63 mmol) in THF (1 ml). Stirredthe reaction mixture at 25° C. for 10 min. The reaction mixture wasquenched with sat.aqueous NH₄Cl (50 ml) and extracted with ethyl acetate(50 ml). The organic layer was separated, dried over Na₂SO₄, filteredand concentrated in vacuo to give 2.1 g of crude compound. This residuewas purified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0-7%) of ethyl acetate inpetroleum ether to afford the title compound (0.81 g, 45.3%) as anoff-white solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.72 (s, 1H), 7.11 (d,J=3.6 Hz, 1H), 6.66-6.57 (m, 2H), 5.94 (d, J=2.6 Hz, 1H), 5.81-5.75 (m,2H), 5.57 (dd, J=6.0, 1.5 Hz, 1H), 5.49 (d, J=10.9 Hz, 1H), 4.66 (dt,J=6.0, 1.0 Hz, 1H), 1.52 (s, 3H), 1.40 (s, 3H); LCMS m/z=318.09 (M+1,100%).

7-((3aS,4R,6aR)-2,2-Dimethyl-6-vinyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4-ethyl-7H-pyrrolo[2,3-d]pyrimidine

To a stirred solution of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine(500 mg, 1.573 mmol) in THF (1 ml) and NMP (0.2 ml) was added ferricacetylacetonate (55.6 mg, 0.157 mmol) at 25° C. 2M Ethylmagnesiumchloride in THF (1.573 ml, 3.15 mmol) was added dropwise and thereaction mixture was stirred for 4 h. The reaction mixture was quenchedwith sat.aqueous NH₄Cl (10 ml) and extracted with ethyl acetate (10 ml).The organic layer was separated, dried over Na₂SO₄, filtered andconcentrated in vacuo to give 0.6 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0-90%) of ethyl acetate inpetroleum ether to afford the title compound (0.28 g, 57.1%) as anoff-white solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.71 (s, 1H), 7.35 (d,J=3.6 Hz, 1H), 6.73 (d, J=3.6 Hz, 1H), 6.60 (dd, J=17.7, 10.8 Hz, 1H),5.88 (d, J=2.7 Hz, 1H), 5.83-5.74 (m, 1H), 5.66-5.56 (m, 2H), 5.45-5.37(m, 1H), 4.67 (dd, J=6.0, 1.1 Hz, 1H), 2.99 (q, J=7.6 Hz, 2H), 1.40 (s,3H), 1.30 (s, 6H); LCMS m/z=312.21 (M+1, 100%).

7-((3aS,4R,6aR)-2,2-Dimethyl-6-vinyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxo-4-yl)-4-isopropyl-7H-pyrrolo[2,3-d]pyrimidine

A solution of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine(1 g, 3.15 mmol), 2M isopropyl magnesium bromide in THF (5.51 ml, 11.01mmol) and PdCl₂(dppf) (0.230 g, 0.315 mmol) in toluene (10 ml) washeated at 100° C. for 30 min. After completion of the reaction, thereaction mixture was quenched with methanol and concentrated. Thisresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution (0-2%) of methanol indichloromethane to afford the title compound (150 mg, 14.65%) as anoff-white solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.98 (s, 1H), 7.48 (d,J=4.0 Hz, 1H), 7.11 (t, J=1.6 Hz, 1H), 6.86 (d, J=4.0 Hz, 1H), 3.98 (dt,J=2.5, 1.2 Hz, 2H), 3.50-3.43 (m, 1H), 2.66 (s, 1H), 2.20 (d, J=2.4 Hz,1H), 2.00 (dd, J=7.2, 1.0 Hz, 2H), 1.44 (dd, J=6.9, 3.1 Hz, 6H), 1.28(s, 6H).

4-Cyclopropyl-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4-ethyl-7H-pyrrolo[2,3-d]pyrimidine. LCMSm/z=323.90 (M+; 100%).

1-((3aS,4R,6aR)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethan-1-ol

To a stirred solution of(3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde(2.30 g, 7.19 mmol) in THF (120 ml) at −78° C., was addedmethylmagnesium bromide (4.80 ml, 14.39 mmol) and the reaction mixturewas stirred at same temperature for 3 h. The reaction mixture wasquenched with a sat. aqueous NH₄Cl (50 ml) and extracted with ethylacetate (50 ml). Layers were separated, the organic layer was washedwith brine (50 ml) and dried over anhydrous sodium sulphate. The organiclayer was filtered and concentrated in vacuo to give 2.2 g of crudecompound and this crude residue was purified by combiflash (Rf200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0 to 20%) of ethyl acetate in petroleum ether to afford thetitle compound (1.82 g, 75%) as a off-white solid. ¹H NMR (400 MHz,Chloroform-d) δ 8.70 (s, 1H), 7.11 (d, J=3.7 Hz, 1H), 6.63 (d, J=3.7 Hz,1H), 5.88-5.81 (m, 1H), 5.80-5.71 (m, 1H), 5.59-5.45 (m, 1H), 4.76-4.64(m, 2H), 1.59-1.49 (m, 6H), 1.38 (d, J=1.0 Hz, 3H), 1.32-1.23 (m, 1H);LCMS m/z=336.2 (M+; 100%).

1-((3aS,4R,6aR)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethan-1-one

To a stirred solution of1-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethan-1-ol(4.75 g, 14.15 mmol) in dichloromethane (45 ml) at 0° C., was addedDess-Martin Periodinane (7.20 g, 16.97 mmol) portion-wise and stirredfor 30 min. Water (50 ml) was added and filtered the reaction mixturethrough a celite bed, washed with dichloromethane (25 ml×2). Separatedthe layers and the organic layer was washed with brine (50 ml), driedover anhydrous sodium sulphate and concentrated in vacuo to give 4.8 gcrude compound. This crude residue was purified by combiflash (Rf200,Teledyne/Isco) instrument onto a Redisep® Rf column with gradientelution (0 to 50%) of ethyl acetate in petroleum ether to afford thetitle compound (3.8 g, 80%) as an off-white solid. ¹H NMR (400 MHz,Chloroform-d) δ 8.68 (s, 1H), 7.10 (d, J=3.7 Hz, 1H), 6.68 (d, J=3.6 Hz,1H), 6.63 (dt, J=2.7, 0.7 Hz, 1H), 5.96 (dt, J=2.8, 1.5 Hz, 1H), 5.75(dd, J=5.9, 1.6 Hz, 1H), 4.82 (dt, J=5.9, 1.1 Hz, 1H), 2.47 (s, 3H),1.52 (s, 3H), 1.39 (s, 3H); LCMS m/z=334.09 (M+; 100%).

2-((3aS,4R,6aR)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)propan-2-ol

To a stirred solution of1-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethan-1-one(1.0 g, 3.00 mmol)) in THF (10 ml) at −20° C., was added dropwise methylmagnesium bromide (1.498 ml, 4.49 mmol) and stirred the reaction mixturefor 30 min at the same temperature. The reaction mixture was quenchedwith a sat. aqueous NH₄Cl (50 ml) and extracted with ethyl acetate (50ml). Layers were separated, the organic layer was washed with brine (50ml) and dried over anhydrous sodium sulphate. The organic layer wasfiltered and concentrated in vacuo to give 1.5 g of crude compound andthis crude residue was purified by combiflash (Rf200, Teledyne/Isco)instrument onto a Redisep® Rf column with gradient elution (0 to 30%) ofethyl acetate in petroleum ether to afford the title compound (850 mg,81%) as an off-white solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.69 (s,1H), 7.09 (d, J=3.6 Hz, 1H), 6.71-6.60 (m, 1H), 5.82 (s, 1H), 5.78-5.69(m, 1H), 5.65-5.58 (m, 1H), 4.69 (dt, J=5.8, 1.0 Hz, 1H), 1.59-1.53 (m,9H), 1.38 (s, 3H); LCMS m/z=350.2 (M+; 100%).

4-Chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-(prop-1-en-2-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

To a stirred solution of2-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)propan-2-ol(8.2 g, 23.44 mmol) in dichloromethane (80 ml) at 0° C. was addedMartin's Sulfurane (17.34 g, 25.8 mmol) and the stirred the reactionmixture for 45 min at 25° C. The reaction mixture was quenched with ansat.aq. sodium bicarbonate (100 ml), extracted with dichloromethane (100ml). Layers were separated, the organic layer was washed with brine (50ml) and was dried over anhydrous sodium sulphate. The organic layer wasfiltered and concentrated in vacuo to give 8.5 g of crude compound. Thiscrude residue was purified by combiflash (Rf200, Teledyne/Isco)instrument onto a Redisep® Rf column with gradient elution (0 to 30%) ofethyl acetate in petroleum ether to afford the title compound (4.2 g,54.0%) as an off-white solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.71 (s,1H), 7.11 (d, J=3.6 Hz, 1H), 6.63 (d, J=3.6 Hz, 1H), 6.00-5.94 (m, 1H),5.76 (d, J=2.7 Hz, 1H), 5.62-5.52 (m, 2H), 5.33 (d, J=1.7 Hz, 1H), 4.67(dt, J=6.0, 1.0 Hz, 1H), 2.03 (t, J=1.0 Hz, 3H), 1.52 (s, 3H), 1.40 (s,3H); LCMS m/z=332.28 (M+; 100%).

7-((3aS,4R,6aR)-2,2-Dimethyl-6-(prop-1-en-2-yl)-4,6a-dihydro-3aH-cyclopenta[d][1,3] dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine

To a degassed solution of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-(prop-1-en-2-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine(1.000 g, 3.01 mmol) in dioxane (10 ml) and water (1 ml), was addedpotassium phosphate, tribasic (1.575 g, 9.04 mmol),dichloro[1,1′-bis(di-t-butylphosphino)ferrocene]palladium(II) (0.196 g,0.301 mmol) and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (4.21 ml,30.1 mmol) at 25° C. The resulting mixture was stirred at 100° C. for 50min under microwave condition. Solvent was removed and the crude residuewas purified by combiflash (Rf200, Teledyne/Isco) instrument onto aRedisep® Rf column with gradient elution (0 to 50%) of ethyl acetate inpetroleum ether to afford the title compound (0.84 g, 90%) as anoff-white solid. LCMS m/z=312.28 (M+1; 100%).

7-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine(A)7-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine(B)

To a degassed solution of7-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine(5 g, 8.93 mmol) in dioxane (80 ml) and water (10 ml), was addedpotassium phosphate tribasic (4.66 g, 26.8 mmol),dichloro[1,1′-bis(di-t-butylphosphino) ferrocene]palladium(II) (0.582 g,0.893 mmol) and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (12.48 ml,89 mmol) at 25° C. The reaction mixture was heated at 80° C. for 8 h.The reaction mixture was diluted with ethyl acetate (50 ml) and washedwith water (50 ml). Layers were separated and the organic layer waswashed with brine (50 ml) and dried over anhydrous sodium sulphate. Theorganic layer was filtered and concentrated in vacuo to give 4.3 g ofcrude compound. This crude residue was purified by combiflash (Rf200,Teledyne/Isco) instrument onto a Redisep® Rf column with gradientelution (0 to 20%) of ethyl acetate in petroleum ether to afford thetitle compound, A (3.2 g, 66%) and B (0.75 g, 15.98%) as an off-whitesolids. ¹H NMR of A (400 MHz, Chloroform-d) δ 8.83 (s, 1H), 7.71 (tt,J=6.6, 1.5 Hz, 4H), 7.48-7.37 (m, 6H), 6.91 (d, J=3.6 Hz, 1H), 6.57 (d,J=3.6 Hz, 1H), 5.88 (s, 2H), 5.25 (d, J=5.7 Hz, 1H), 4.60 (d, J=5.7 Hz,1H), 4.55-4.45 (m, 2H), 2.77 (s, 3H), 1.45 (s, 3H), 1.32 (s, 3H), 1.11(s, 9H); LCMS m/z=540.4 (M+1; 100%); ¹H NMR of B (400 MHz, Chloroform-d)δ 7.71 (tt, J=6.6, 1.5 Hz, 4H), 7.53-7.35 (m, 6H), 6.98 (d, J=3.6 Hz,1H), 6.57 (d, J=3.6 Hz, 1H), 5.90 (d, J=14.5 Hz, 2H), 5.26 (d, J=5.7 Hz,1H), 4.61 (d, J=5.7 Hz, 1H), 4.51 (d, J=9.3 Hz, 2H), 1.46 (s, 3H), 1.33(s, 3H), 1.28 (s, 2H), 1.11 (s, 9H); LCMS m/z=526.44 (M+1; 100%).

((3aS,4R,6aR)-2,2-dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methanol

To a stirred solution of7-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine(3.20 g, 5.93 mmol) in THF (20 ml), was slowly added TBAF (8.89 ml, 8.89mmol) at 25° C. and stirred the reaction mixture at 25° C. for 15 h.Volatiles were removed in vacuo and the crude residue was purified bycombiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0 to 100%) of ethyl acetate in petroleumether to afford the title compound (1.5 g, 84%) as an off-white solid.¹H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 1H), 7.06 (d, J=3.6 Hz, 1H),6.55 (d, J=3.6 Hz, 1H), 5.90-5.78 (m 2H), 5.41 (ddd, J=5.8, 1.7, 0.9 Hz,1H), 4.65 (dt, J=5.8, 0.9 Hz, 1H), 4.56-4.42 (m, 2H), 3.35 (d, J=8.2 Hz,1H), 2.74 (s, 3H), 1.53 (s, 3H), 1.37 (s, 3H); LCMS m/z=302.21 (M+1;100%).

(3aS,4R,6aR)-2,2-Dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde

To a stirred solution of7-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine (1.50 g, 4.98 mmol) in dichloromethane (100 ml) at 0°C., was added Dess-Martin Periodinane (2.53 g, 5.97 mmol) portion-wiseand stirred for 1 h. The reaction mixture was diluted with methylenechloride (50 ml) and washed with water (50 ml). Layers were separated,the organic layer was washed with brine (50 ml) and dried over anhydroussodium sulphate. The organic layer was filtered and concentrated invacuo to give a crude compound and this crude residue was purified bycombiflash (Rf200, Teledyne/Isco) instrument onto a Redisep® Rf columnwith gradient elution (0 to 30%) of ethyl acetate in petroleum ether toafford the title compound (0.95 g, 63.8%) as an off-white solid. ¹H NMR(400 MHz, Chloroform-d) δ 10.00 (s, 1H), 8.80 (s, 1H), 7.02 (d, J=3.6Hz, 1H), 6.82-6.76 (m, 1H), 6.63 (d, J=3.6 Hz, 1H), 6.00 (dt, J=2.7, 1.4Hz, 1H), 5.76 (dd, J=5.9, 1.5 Hz, 1H), 4.87 (dt, J=5.9, 1.1 Hz, 1H),2.77 (s, 3H), 1.53 (s, 3H), 1.38 (s, 3H); LCMS m/z=300.15 (M+1; 100%)

7-((3aS,4R,6aR)-2,2-Dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxo-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR (400 MHz, Chloroform-d)δ 8.83 (s, 1H), 7.01 (d, J=3.6 Hz, 1H), 6.68-6.53 (m, 2H), 5.95 (d,J=2.5 Hz, 1H), 5.80-5.71 (m, 2H), 5.56 (dd, J=6.0, 1.4 Hz, 1H), 5.47 (d,J=10.8 Hz, 1H), 4.65 (d, J=5.8 Hz, 1H), 2.75 (s, 3H), 1.52 (s, 3H), 1.40(s, 3H); LCMS m/z=298.5 (M+1; 100%).

((3aS,4R,6aR)-2,2-Dimethyl-4-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methanol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of7-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine.LCMS m/z=287.90 (M+; 100%).

(3aS,4R,6aR)-2,2-Dimethyl-4-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-Dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.¹H NMR (400 MHz, Chloroform-d) δ 10.01 (s, 1H), 9.04 (s, 1H), 8.93 (s,1H), 7.11 (d, J=3.6 Hz, 1H), 6.83-6.77 (m, 1H), 6.67 (d, J=3.7 Hz, 1H),6.03 (dt, J=2.8, 1.4 Hz, 1H), 5.77 (dd, J=5.9, 1.5 Hz, 1H), 4.89 (dt,J=6.0, 1.2 Hz, 1H), 1.54 (s, 3H), 1.41 (s, 3H); LCMS m/z=286.09 (M+;100%).

7-((3aS,4R,6aR)-2,2-Dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR (400 MHz, Chloroform-d)δ 8.97 (d, J=15.8 Hz, 2H), 7.09 (d, J=3.7 Hz, 1H), 6.68-6.56 (m, 2H),5.98 (d, J=2.7 Hz, 1H), 5.82-5.72 (m, 2H), 5.60-5.54 (m, 1H), 5.52-5.44(m, 1H), 4.66 (dt, J=5.8, 1.0 Hz, 1H), 1.52 (s, 3H), 1.40 (s, 3H); LCMSm/z=284.04 (M+1; 100%).

7-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine

To a stirred solution of(3aS,4S,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-ol (3.5 g, 8.24 mmol) in THF (50 ml) was added4-chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine (3.54 g, 20.61 mmol, whichwas synthesized by following the same reaction protocol as was describedin WO2005/16878, A2), triphenylphosphine (5.40 g, 20.61 mmol), DIAD(4.01 ml, 20.61 mmol) at 0° C. and stirred for 30 min. The resultingreaction mixture was stirred at 25° C. for 16 h. Volatiles were removedin vacuo and the crude residue was purified by combiflash (Rf200,Teledyne/Isco) instrument onto a Redisep® Rf column with gradientelution (0 to 10%) of ethyl acetate in petroleum ether to afford thetitle compound (2.7 g, 56.7%) as an off-white solid. LCMS m/z=577.94(M+; 100%).

((3aR,6R,6aS)-6-(4-Chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of7-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine.LCMS m/z=340.03 (M+; 100%).

(3aR,6R,6aS)-6-(4-Chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxole-4-carbaldehyde

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-Dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.¹H NMR (400 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.73 (s, 1H), 7.80 (d, J=2.0Hz, 1H), 7.10-7.03 (m, 1H), 6.01 (dq, J=2.7, 1.4 Hz, 1H), 5.57 (dd,J=6.0, 1.5 Hz, 1H), 4.80 (dt, J=6.0, 1.2 Hz, 1H), 1.39 (s, 3H), 1.28 (s,3H); LCMS m/z=338.03 (M+; 100%).

4-Chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR (400 MHz, DMSO-d₆) δ8.71 (s, 1H), 7.66 (d, J=2.0 Hz, 1H), 6.66-6.52 (m, 1H), 5.90-5.78 (m,2H), 5.67-5.55 (m, 2H), 5.47-5.36 (m, 1H), 4.71 (d, J=6.0 Hz, 1H), 1.38(s, 3H), 1.31 (s, 3H); LCMS m/z=336.03 (M+; 100%).

7-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-2-chloro-7H-pyrrolo[2,3-d]pyrimidine

To a stirred solution of(3aS,4S,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-ol(1.2 g, 2.83 mmol) in THF (15 ml) was added2-chloro-7H-pyrrolo[2,3-d]pyrimidine (0.738 g, 4.80 mmol),triphenylphosphine (2.59 g, 9.89 mmol) and DIAD (1.923 ml, 9.89 mmol)slowly at 0° C. and stirred for 5 mins. The reaction mixture was broughtto 25° C. and stirred for 1 h. Volatiles were removed in vacuo and thecrude residue was purified by combiflash (Rf200, Teledyne/Isco)instrument onto a Redisep® Rf column with gradient elution (0 to 15%) ofethyl acetate in petroleum ether to afford the title compound (1.1 g,69.5%) as an off-white solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.84 (s,1H), 7.70 (ddt, J=6.6, 5.0, 1.5 Hz, 4H), 7.50-7.34 (m, 6H), 6.94 (d,J=3.6 Hz, 1H), 6.59 (d, J=3.6 Hz, 1H), 5.84 (dt, J=19.8, 2.2 Hz, 2H),5.30 (d, J=5.7 Hz, 1H), 4.63 (d, J=5.6 Hz, 1H), 4.57-4.42 (m, 2H), 1.43(s, 3H), 1.33 (s, 3H), 1.10 (s, 9H); LCMS m/z=560.3 (M+; 100).

((3aR,6R,6aS)-6-(2-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

To a stirred solution of7-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-2-chloro-7H-pyrrolo[2,3-d]pyrimidine(500 mg, 0.893 mmol) in THF (5 ml) at 0° C., was added TBAF (1.250 ml,1.250 mmol) slowly and stirred the reaction mixture at the sametemperature for 10 min. The reaction mixture was brought to 25° C. andstirred for 30 mins. Volatiles were removed in vacuo and the cruderesidue was purified by combiflash (Rf200, Teledyne/Isco) instrumentonto a Redisep® Rf column with gradient elution (0 to 40%) of ethylacetate in petroleum ether to afford the title compound (0.27 g, 94%) asa colourless oil. ¹H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 1H), 7.28(s, 1H), 7.08 (d, J=3.7 Hz, 1H), 6.57 (d, J=3.7 Hz, 1H), 5.92-5.62 (m,2H), 5.47 (d, J=5.7 Hz, 1H), 4.69 (dt, J=5.6, 0.9 Hz, 1H), 4.59-4.37 (m,2H), 1.52 (s, 3H), 1.38 (s, 3H); LCMS m/z=321.09 (M+; 100).

(3aR,6R,6aS)-6-(2-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxole-4-carbaldehyde

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-Dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.¹H NMR (400 MHz, Chloroform-d) δ 9.99 (s, 1H), 8.86 (s, 1H), 7.04 (d,J=3.7 Hz, 1H), 6.75 (dd, J=2.6, 0.9 Hz, 1H), 6.65 (d, J=3.7 Hz, 1H),6.00 (dt, J=2.7, 1.4 Hz, 1H), 5.77 (dd, J=5.9, 1.5 Hz, 1H), 4.88 (dd,J=5.9, 1.2 Hz, 1H), 1.53 (s, 3H), 1.40 (s, 3H); LCMS m/z=319.90 (M+;100).

2-Chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesize by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR (400 MHz, Chloroform-d)δ 8.82 (s, 1H), 7.03 (d, J=3.6 Hz, 1H), 6.64-6.53 (m, 2H), 5.93 (d,J=2.6 Hz, 1H), 5.81-5.69 (m, 2H), 5.60 (dd, J=5.8, 1.4 Hz, 1H),5.53-5.44 (m, 1H), 4.68 (dd, J=5.8, 1.1 Hz, 1H), 1.45 (s, 6H); LCMSm/z=318.15 (M+; 100).

1-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-1H-pyrrolo[3,2-c]pyridine

To a stirred solution of(3aS,4S,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-ol (0.5 g, 1.178 mmol) in THF (7 ml) at 0° C. wasadded 4-chloro-H-pyrrolo[3,2-c]pyridine (0.305 g, 2.002 mmol),triphenylphosphine (1.081 g, 4.12 mmol) and DIAD (0.801 ml, 4.12 mmol)slowly and stirred for 5 min. The reaction mixture was stirred at 25° C.for 16 h. Volatiles were removed in vacuo and the crude residue waspurified by combiflash (Rf200, Teledyne/Isco) instrument onto a Redisep®Rf column with gradient elution (0 to 10%) of ethyl acetate in petroleumether to afford the title compound (0.3 g, 45.6%) as an off-white solid.LCMS m/z=559.23 (M+; 100).

((3aR,6R,6aS)-6-(4-Chloro-1H-pyrrolo[3,2-c]pyridin-1-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

To a stirred solution of1-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-1H-pyrrolo[3,2-c]pyridine(1.3 g, 2.325 mmol) in THF (13 ml) was added TBAF (3.25 ml, 3.25 mmol)at 0° C. and stirred for 5 mins. The reaction mixture was brought to 25°C. and stirred for 1 h. Volatiles were removed in vacuo and the cruderesidue was purified by combiflash (Rf200, Teledyne/Isco) instrumentonto a Redisep® Rf column with gradient elution (0 to 45%) of ethylacetate in petroleum ether to afford the title compound (0.5 g, 67%) asan off-white solid. LCMS m/z=319.71 (M−1; 100).

(3aR,6R,6aS)-6-(4-Chloro-1H-pyrrolo[3,2-c]pyridin-1-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxole-4-carbaldehyde

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-Dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.¹H NMR (400 MHz, Chloroform-d) δ 10.05 (s, 1H), 8.19 (d, J=5.8 Hz, 1H),7.34 (dd, J=5.9, 0.9 Hz, 1H), 6.99 (d, J=3.3 Hz, 1H), 6.94-6.89 (m, 1H),6.74 (dd, J=3.3, 0.9 Hz, 1H), 5.73-5.58 (m, 2H), 4.67 (dt, J=5.9, 1.2Hz, 1H), 1.55 (s, 3H), 1.39 (s, 3H); LCMS m/z=319.05 (M+; 100).

4-Chloro-1-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-pyrrolo[3,2-c]pyridine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR (400 MHz, Chloroform-d)δ 8.14 (d, J=5.8 Hz, 1H), 7.37 (dd, J=5.9, 0.9 Hz, 1H), 7.06 (d, J=3.3Hz, 1H), 6.70-6.59 (m, 2H), 5.91-5.72 (m, 2H), 5.55-5.48 (m, 3H),4.59-4.47 (m, 1H), 1.53 (s, 3H), 1.40 (s, 3H); LCMS m/z=317.15 (M+;100).

1-((3aS,4R,6aR)-2,2-Dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-methyl-1H-pyrrolo[3,2-c]pyridine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of7-((3aS,4R,6aR)-2,2-dimethyl-6-(prop-1-en-2-yl)-4,6a-dihydro-3aH-cyclopenta[d][1,3] dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine. LCMSm/z=297.21 (M+; 100). Des chloro compound i.e.1-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-1H-pyrrolo[3,2-c]pyridinewas also formed, which was separated after Suzuki coupling step(Table-6) by reverse phase preparative HPLC.

(3aR,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-5-iodo-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-one

To a stirred solution of(3aR,6a-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-one(20 g, 47.3 mmol) and iodine (14.41 g, 56.8 mmol) in dichloromethane(250 ml), was added pyridine (3.45 ml, 42.6 mmol) under nitrogenatmosphere at 0° C. and stirred at 25° C. for 4 h. The reaction mixturewas diluted with methylene chloride (100 ml) and washed with a saturatedaqueous sodium thiosulfate (100 ml). Layers were separated, the organiclayer was washed with brine (100 ml) and dried over anhydrous sodiumsulphate. The organic layer was filtered and concentrated in vacuo togive 18 g of crude compound. This crude residue was purified bycombiflash (Rf200, Teledyne/Isco) instrument onto a Redisep® Rf columnwith gradient elution (0 to 20%) of ethyl acetate in petroleum ether toafford the title compound (15 g, 57.8%) as a colorless oil. ¹H NMR (400MHz, Chloroform-d) δ 7.74 (ddt, J=17.2, 6.5, 1.6 Hz, 4H), 7.58-7.36 (m,6H), 5.19 (d, J=5.8 Hz, 1H), 4.79 (t, J=5.6 Hz, 1H), 4.53-4.33 (m, 2H),1.45 (s, 3H), 1.35 (s, 3H), 1.08 (s, 9H).

(3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-5-iodo-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-ol

To a stirred solution of(3aR,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-5-iodo-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-one(13.7 g, 24.98 mmol) in methanol (130 ml), was added cerium (III)chloride heptahydrate (10.24 g, 27.5 mmol) at 0° C. and the reactionmixture was stirred for 30 min. Sodium borohydride (0.992 g, 26.2 mmol)was added portion-wise and the resulting mixture was stirred at 0° C.for 2 h under N₂ atmosphere. The reaction mass was quenched with water(150 ml) and extracted with ethyl acetate (150 ml×2). The combinedorganic layer was washed with brine (100 ml), dried over sodium sulfate& concentrated to give 8.5 g of crude compound. This residue waspurified by combiflash (Rf200, Teledyne/Isco) instrument onto a Redisep®Rf column with gradient elution (0 to 20%) of ethyl acetate in petroleumether to afford the title compound (6 g, 43.6%) as a colorless oil. ¹HNMR (400 MHz, Chloroform-d) δ 7.84-7.62 (m, 4H), 7.48-7.39 (m, 6H), 5.19(d, J=5.8 Hz, 1H), 4.86-4.71 (m, 1H), 4.46-4.31 (m, 3H), 2.84 (d, J=10.3Hz, 1H), 1.45 (s, 3H), 1.38-1.33 (s, 3H), 1.08 (s 9H).

7-((3aS,4S,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-5-iodo-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of1-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-1H-pyrrolo[3,2-c]pyridine. ¹H NMR (400 MHz, Chloroform-d) δ 8.64 (s, 1H), 7.75 (ddt,J=20.3, 6.8, 1.5 Hz, 4H), 7.53-7.31 (m, 6H), 6.96 (d, J=3.7 Hz, 1H),6.67 (d, J=3.6 Hz, 1H), 5.74-5.62 (m, 2H), 4.86-4.80 (m, 1H), 4.54-4.42(m, 2H), 1.48 (s, 3H), 1.42 (s, 3H), 1.13 (s, 9H).

LCMS m/z=686.33 (M+; 100).

7-((3aS,4S,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-5-iodo-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-N-(4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

A mixture of7-((3aS,4S,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-5-iodo-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine(1.7 g, 2.478 mmol) and (4-methoxyphenyl)methanamine (3.40 g, 24.78mmol) in ethanol (1.7 ml) was refluxed for 4 h. The reaction mixture wasquenched with water (150 ml) and extracted with ethyl acetate (150 ml).The combined organic layer was washed with brine (100 ml), dried oversodium sulfate and concentrated to give 8.5 g of crude compound. Thisresidue was purified by combiflash (Rf200, Teledyne/Isco) instrumentonto a Redisep® Rf column with gradient elution (0 to 40%) of ethylacetate in petroleum ether to afford the title compound (1.8 g, 92%) asan off white solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.37 (d, J=6.4 Hz,1H), 7.76 (ddt, J=19.4, 6.8, 1.4 Hz, 4H), 7.52-7.32 (m, 8H), 7.00-6.88(m, 2H), 6.67 (d, J=3.7 Hz, 1H), 6.42 (d, J=3.6 Hz, 1H), 5.71 (s, 1H),5.61 (d, J=6.2 Hz, 1H), 4.80 (dd, J=12.7, 5.8 Hz, 3H), 4.60-4.37 (m,2H), 3.84 (s, 3H), 3.77 (s, 1H), 1.46 (s, 3H), 1.41 (s, 3H), 1.13 (s,9H); LCMS m/z=786.41 (M+; 100).

7-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2,5-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-N-(4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

A mixture of7-((3aS,4S,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-5-iodo-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-N-(4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (3.2 g, 4.07 mmol),2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (1.021 g, 8.13 mmol) andpotassium Carbonate (2.53 g, 18.30 mmol) in DMF (10 ml) was purged withnitrogen for 10 min in a seal tube. Pd(PPh₃)₄ (0.470 g, 0.407 mmol) wasadded to reaction mixture and stirred at 80° C. for 8 h. The reactionmixture was diluted with water (50 ml) and extracted with ethyl acetate(50 ml×2). The combined organic layer was washed with brine (50 ml),dried over sodium sulfate, concentrated in vacuo to give 3.1 g of crudecompound. This residue was purified by combiflash (Rf200, Teledyne/Isco)instrument onto a Redisep® Rf column with gradient elution (0 to 40%) ofethyl acetate in petroleum ether to afford the title compound (2.7 g,98%) as an off-white solid. LCMS m/z=675.60 (M+; 100).

((3aS,4R,6aR)-4-(4-((4-Methoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,5-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methanol

To a stirred solution of7-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2,5-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-N-(4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (2.7 g, 4.00 mmol) in THF (40 ml) at 0° C., wasadded TBAF (4.80 ml, 4.80 mmol) slowly and stirred for 2 h at 25° C. Thereaction mixture was diluted with water (50 ml) and extracted with ethylacetate (50 ml×2). The combined organic layer was washed with brine (50ml), dried over sodium sulfate, filtered and concentrated in vacuo togive 2.2 g of crude compound. This residue was purified by combiflash(Rf200, Teledyne/Isco) instrument onto a Redisep® Rf column withgradient elution (0 to 100%) of ethyl acetate in petroleum ether toafford the title compound (1.7 g, 97%) as a colorless oil. ¹H NMR (400MHz, Chloroform-d) δ 7.69 (ddd, J=12.0, 8.3, 1.4 Hz, 1H), 7.62-7.41 (m,1H), 7.41-7.30 (m, 2H), 6.99-6.80 (m, 2H), 6.70 (d, J=3.6 Hz, 1H), 6.35(d, J=3.5 Hz, 1H), 5.67 (s, 1H), 5.51 (d, J=5.9 Hz, 1H), 4.79 (d, J=5.5Hz, 2H), 4.60 (dd, J=5.9, 0.9 Hz, 1H), 4.45 (s, 2H), 3.83 (s, 3H), 1.61(t, J=1.1 Hz, 3H), 1.51 (s, 3H), 1.37 (s, 3H). LCMS m/z=437.17 (M+,100%).

((3aS,4R,6aR)-4-(4-((4-Methoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,5-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methyl4-methylbenzeneulfonate

To a mixture of(3aS,4R,6aR)-4-(4-((4-methoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,5-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methanol(100 mg, 0.229 mmol), DMAP (5.60 mg, 0.046 mmol) and TEA (0.096 ml,0.687 mmol) in CH₂Cl₂ (10 ml) at 0° C., was added a solution ofp-toluene sulphonyl chloride (65.5 mg, 0.344 mmol) in CH₂Cl₂ (1 ml) andstirred for 1 h at 25° C. The reaction mixture was diluted with water (5ml) and extracted with ethyl acetate (10 ml×2). The combined organiclayer was washed with brine (10 ml), dried over sodium sulfate, filteredand concentrated in vacuo to give 0.2 g of crude compound. This residuewas purified by combiflash (Rf200, Teledyne/Isco) instrument onto aRedisep® Rf column with gradient elution (0 to 40%) of ethyl acetate inpetroleum ether to afford the title compound (0.08 g, 59.1%) as acolorless oil. Obtained product was used as such for next step withoutcharacterization.

(3aS,4R,6aS)-5-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2,4-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-ol

To a stirred solution of(3aS,6aS)-5-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-one(10.0 g, 23.66 mmol) [synthesized by following the same reactionprotocol as was described in J Org. Chem. 2014, 79, 8059-8066] in THF(100 ml), was added 3M methyl magnesium bromide in THF (11.85 ml, 35.5mmol) at 0° C. The reaction mixture was stirred at 0° C. for 1 h. Thereaction mixture was quenched with a saturated aqueous ammonium chloride(100 ml) and extracted with ethyl acetate (200 ml×2). The combinedorganic layer was washed with brine (50 ml), dried over sodium sulfate,filtered and concentrated in vacuo to give 9.8 g of crude compound. Thisresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution (0 to 20%) of ethylacetate in petroleum ether to afford the title compound (8.50 g, 82%) asa colorless oil. ¹H NMR (400 MHz, Chloroform-d) δ 7.72-7.67 (m, 4H),7.47-7.37 (m, 6H), 5.84 (q, J=2.0 Hz, 1H), 5.11-5.00 (m, 1H), 4.46-4.28(m, 3H), 3.51 (s, 1H), 1.47 (s, 3H), 1.42 (s, 3H), 1.26 (s, 3H), 1.09(s, 9H).

(3aS,4S,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2,6a-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-ol

To a stirred solution of(3aS,4R,6aS)-5-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2,4-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-ol(8.0 g, 18.24 mmol) in anhydrous acetone (80 ml), was added p-TsOH H₂O(0.69 g, 3.65 mmol) at 25° C. and stirred for 18 h. TLC showed 50%conversion. The reaction mixture was then concentrated in vacuo, dilutedwith methylene chloride (100 ml) and washed with saturated NaHCO₃ (50ml). Layers were separated, the organic layer was washed with brine (50ml) and dried over anhydrous sodium sulphate. The organic layer wasfiltered and concentrated in vacuo to give 4.5 g of crude compound. Thisresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution (0 to 30%) of ethylacetate in petroleum ether to afford the title compound (3.5 g, 43%) asan oil. ¹H NMR (400 MHz, Chloroform-d) δ 7.74-7.65 (m, 4H), 7.48-7.35(m, 6H), 5.81 (p, J=1.6 Hz, 1H), 4.62-4.55 (m, 1H), 4.44-4.24 (m, 3H),1.39 (s, 3H), 1.34 (s, 3H), 1.29 (s, 3H), 1.10 (s, 9H).

7-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2,6a-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of1-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-1H-pyrrolo[3,2-c]pyridine. ¹H NMR (400 MHz, Chloroform-d) δ 8.74 (s, 1H), 7.78-7.67 (m,4H), 7.52-7.39 (m, 6H), 6.94 (d, J=3.6 Hz, 1H), 6.61 (d, J=3.6 Hz, 1H),5.94-5.86 (m, 1H), 5.80 (q, J=2.4 Hz, 1H), 4.62-4.48 (m, 2H), 4.13 (d,J=1.2 Hz, 1H), 1.39 (s, 3H), 1.38 (s, 3H), 1.36 (s, 3H), 1.13 (s, 9H),LCMS m/z=574.44 (M+; 100%).

((3aS,4R,6aR)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,6a-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methanol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of((3aR,6R,6aS)-6-(2-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol.¹H NMR (400 MHz, Chloroform-d) δ 8.73 (s, 1H), 7.16 (d, J=3.6 Hz, 1H),6.62 (d, J=3.6 Hz, 1H), 5.87-5.78 (m, 2H), 4.62-4.44 (m, 2H), 4.25-4.20(m, 1H), 1.56 (s, 3H), 1.49 (s, 3H), 1.42 (s, 3H); LCMS m/z=336.15 (M+;100%).

(3aS,4R,6aR)-4-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,6a-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.¹H NMR (400 MHz, Chloroform-d) δ 10.01 (s, 1H), 8.73 (s, 1H), 7.09 (d,J=3.6 Hz, 1H), 6.78 (dd, J=2.8, 1.2 Hz, 1H), 6.69 (d, J=3.6 Hz, 1H),5.99 (dd, J=2.8, 0.8 Hz, 1H), 4.34 (t, J=0.8 Hz, 1H), 1.78 (s, 3H), 1.47(s, 3H), 1.44 (s, 3H), LCMS m/z=334.22 (M+1; 100%).

4-Chloro-7-((3aS,4R,6aR)-2,2,6a-trimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR (400 MHz, Chloroform-d)δ 8.74 (s, 1H), 7.16 (d, J=3.6 Hz, 1H), 6.62 (d, J=3.6 Hz, 1H), 6.49(dd, J=17.6, 11.2 Hz, 1H), 5.94-5.87 (m, 1H), 5.85-5.76 (m, 2H), 5.47(dd, J=11.2, 1.2 Hz, 1H), 4.15 (d, J=1.1 Hz, 1H), 1.60 (s, 3H), 1.44 (s,6H), LCMS m/z=332.22 (M+1; 100%).

7-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2,6a-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of7-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR1 (400 MHz, Chloroform-d) δ 8.86 (s, 1H), 7.73(ddt, J=15.2, 6.7, 1.5 Hz, 4H), 7.52-7.39 (m, 6H), 6.90 (d, J=3.6 Hz,1H), 6.55 (dd, J=3.7, 2.3 Hz, 1H), 5.90 (dt, J=2.9, 1.5 Hz, 1H), 5.82(q, J=2.4 Hz, 1H), 4.54 (dq, J=6.2, 1.8 Hz, 2H), 4.14 (dd, J=6.7, 2.1Hz, 1H), 1.64 (s, 6H), 1.39 (s, 3H), 1.36 (d, J=2.1 Hz, 3H), 1.12 (s,9H); LCMS m/z=554.32 (M+, 100%).

((3aS,4R,6aR)-2,2,6a-Trimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methanol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of((3aR,6R,6aS)-6-(2-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol.¹H NMR (400 MHz, Chloroform-d) δ 8.86 (s, 1H), 7.08 (d, J=3.7 Hz, 1H),6.57 (dd, J=3.6, 1.1 Hz, 1H), 5.86-5.78 (m, 2H), 4.59-4.47 (m, 2H), 4.23(dt, J=6.9, 0.8 Hz, 1H), 2.77 (s, 3H), 1.56 (s, 3H), 1.50 (s, 3H), 1.42(s, 3H); LCMS m/z=316.21 (M+, 100%).

(3aS,4R,6aR)-2,2,6a-Trimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.¹H NMR (400 MHz, Chloroform-d) δ 10.01 (s, 1H), 8.87 (s, 1H), 7.03 (d,J=3.7 Hz, 1H), 6.79 (td, J=2.8, 1.1 Hz, 1H), 6.67 (d, J=3.7 Hz, 1H),6.02 (dd, J=2.9, 0.7 Hz, 1H), 4.33 (d, J=0.9 Hz, 1H), 2.82 (s, 3H), 1.78(s, 3H), 1.47 (s, 3H), 1.44 (s, 3H); LCMS m/z=314.28 (M+, 100%).

(4-Methyl-7-((3aS,4R,6aR)-2,2,6a-trimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR (400 MHz, Chloroform-d)δ 8.87 (s, 1H), 7.09 (d, J=3.7 Hz, 1H), 6.60-6.44 (m, 2H), 5.94-5.75 (m,3H), 5.45 (dd, J=11.3, 1.5 Hz, 1H), 4.21-4.07 (m, 1H), 2.78 (s, 3H),2.64 (s, 3H), 1.44 (s, 6H); LCMS m/z=312.28 (M+, 100%).

1-((3aR,6R,6aS)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,3a-trimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)ethanol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of1-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethan-1-ol.¹H NMR (400 MHz, Chloroform-d) δ 8.73 (d, J=2.0 Hz, 1H), 7.12 (dd,J=31.8, 3.6 Hz, 1H), 6.62 (t, J=3.3 Hz, 1H), 5.87-5.76 (m, 2H),4.78-4.68 (m, 2H), 4.26-4.20 (m, 1H), 1.61 (d, J=7.1 Hz, 3H), 1.54 (s,6H), 1.43 (d, J=3.5 Hz, 3H); LCMS m/z=350.22 (M+, 100%).

1-((3aR,6R,6aS)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,3a-trimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)ethanone

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of1-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethan-1-one.¹H NMR (400 MHz, Chloroform-d) δ 8.74 (s, 1H), 7.10 (d, J=3.7 Hz, 1H),6.74-6.56 (m, 2H), 5.95 (d, J=2.9 Hz, 1H), 4.27 (t, J=0.9 Hz, 1H), 2.49(s, 3H), 1.76 (s, 3H), 1.48 (s, 6H); LCMS m/z=348.16 (M+, 100%).

2-((3aR,6R,6aS)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,3a-trimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)propan-2-ol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of2-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)propan-2-ol.LCMS m/z=364.22 (M+, 100%).

4-Chloro-7-((3aS,4R,6aR)-2,2,6a-trimethyl-6-(prop-1-en-2-yl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-(prop-1-en-2-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine.¹H NMR (400 MHz, Chloroform-d) δ 8.74 (s, 1H), 7.15 (d, J=3.6 Hz, 1H),6.62 (d, J=3.7 Hz, 1H), 5.84 (d, J=3.0 Hz, 1H), 5.76 (ddd, J=12.2, 2.4,1.0 Hz, 2H), 5.31 (t, J=1.6 Hz, 1H), 4.15-4.13 (m, 1H), 2.05 (t, J=1.0Hz, 3H), 1.61 (s, 3H), 1.43 (s, 6H); LCMS m/z=346.02 (M+, 100%).

4-Methyl-7-((3aS,4R,6aR)-2,2,6a-trimethyl-6-(prop-1-en-2-yl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of7-((3aS,4R,6aR)-2,2-dimethyl-6-(prop-1-en-2-yl)-4,6a-dihydro-3aH-cyclopenta[d][1,3] dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR(400 MHz, Chloroform-d) δ 8.87 (s, 1H), 7.06 (d, J=3.6 Hz, 1H), 6.56 (d,J=3.6 Hz, 1H), 5.89-5.67 (m, 3H), 5.29 (t, J=1.6 Hz, 1H), 4.14 (d, J=1.3Hz, 1H), 2.76 (s, 3H), 2.05 (t, J=1.0 Hz, 3H), 1.61 (s, 3H), 1.43 (s,6H); LCMS m/z=326.28 (M+, 100%).

7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-4-(1-methyl-1H-pyrazol-4-)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of7-((3aS,4R,6aR)-2,2-dimethyl-6-(prop-1-en-2-yl)-4,6a-dihydro-3aH-cyclopenta[d][1,3] dioxol-4-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine. LCMSm/z=364.22 (M+, 100%).

(3aS,4R,6aS)-5-(((tert-Butyldiphenylsilyl)oxy)methyl)-4-ethyl-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aS)-5-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2,4-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-ol.¹H NMR (400 MHz, Chloroform-d) δ 7.76-7.74 (m, 2H), 7.73-7.68 (m, 4H),7.44-7.39 (m, 8H), 5.95 (d, J=1.9 Hz, 1H), 5.01 (ddt, J=5.5, 2.9, 1.5Hz, 1H), 4.43-4.36 (m, 2H), 1.49 (s, 3H), 1.43 (s, 3H), 1.10 (s, 9H),0.74 (t, J=7.5 Hz, 3H).

(3aS,4S,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-6a-ethyl-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4S,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2,6a-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-ol.¹H NMR (400 MHz, Chloroform-d) δ 7.72-7.67 (m, 4H), 7.41 (dddt, J=15.6,7.9, 6.7, 2.1 Hz, 6H), 5.92 (p, J=1.7 Hz, 1H), 4.52 (s, 1H), 4.43-4.35(m, 2H), 4.22 (ddd, J=15.6, 3.0, 2.0 Hz, 1H), 2.71 (s, 1H), 1.79-1.64(m, 2H), 1.39 (s, 3H), 1.32 (s, 3H), 1.10 (s, 9H), 0.74 (t, J=7.6 Hz,3H).

7-((3aS,4R,6aR)-6-(((tert-Butyldiphenylsilyl)oxy)methyl)-6a-ethyl-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of1-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-1H-pyrrolo[3,2-c]pyridine. ¹H NMR (400 MHz, Chloroform-d) δ 8.76 (s, 1H), 7.79-7.67 (m,4H), 7.55-7.37 (m, 6H), 6.99 (d, J=3.6 Hz, 1H), 6.60 (d, J=3.6 Hz, 1H),6.03-5.96 (m, 1H), 5.78 (q, J=2.5 Hz, 1H), 4.61-4.43 (m, 2H), 4.25 (d,J=0.9 Hz, 1H), 1.75 (q, J=7.3 Hz, 1H), 1.55 (dq, J=14.8, 7.4 Hz, 1H),1.41 (s, 6H), 1.13 (s, 9H), 0.68 (t, J=7.4 Hz, 3H); LCMS m/z=588.21 (M+,100%).

((3aR,6R,6aS)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a-ethyl-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of((3aR,6R,6aS)-6-(2-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol.¹H NMR (400 MHz, Chloroform-d) δ 8.74 (s, 1H), 7.17 (d, J=3.7 Hz, 1H),6.60 (d, J=3.6 Hz, 1H), 5.93 (dq, J=2.7, 1.5 Hz, 1H), 5.79 (q, J=2.2 Hz,1H), 4.60-4.43 (m, 2H), 4.32 (t, J=0.8 Hz, 1H), 1.94 (dq, J=14.8, 7.4Hz, 1H), 1.74 (dq, J=14.7, 7.5 Hz, 1H), 1.51 (s, 3H), 1.41 (s, 3H), 0.83(t, J=7.5 Hz, 3H); LCMS m/z=350.22 (M+, 100%).

(3aR,6R,6aS)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a-ethyl-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxole-4-carbaldehyde

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.¹H NMR (400 MHz, Chloroform-d) δ 10.02 (s, 1H), 8.75 (s, 1H), 7.09 (d,J=3.7 Hz, 1H), 6.88 (dd, J=2.8, 1.1 Hz, 1H), 6.68 (d, J=3.6 Hz, 1H),5.98 (dd, J=2.8, 1.0 Hz, 1H), 4.43 (d, J=1.0 Hz, 1H), 2.24 (dq, J=14.9,7.5 Hz, 1H), 1.97 (dq, J=14.8, 7.4 Hz, 1H), 1.47 (s, 6H), 0.89 (t, J=7.5Hz, 3H); LCMS m/z=348.22 (M+, 100%).

4-Chloro-7-((3aS,4R,6aR)-6a-ethyl-2,2-dimethyl-6-vinyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR (400 MHz, Chloroform-d)δ 8.75 (s, 1H), 7.16 (d, J=3.7 Hz, 1H), 6.60 (d, J=3.7 Hz, 1H),6.56-6.36 (m, 1H), 5.99-5.69 (m, 3H), 5.44 (dd, J=11.3, 1.5 Hz, 1H),4.25 (d, J=0.9 Hz, 1H), 2.15-1.99 (m, 1H), 1.76 (dq, J=14.8, 7.5 Hz,1H), 1.46 (s, 6H), 0.81 (t, J=7.5 Hz, 3H). LCLCMS m/z=346.22 (M+, 100%).

((3aR,3bR,4aS,5R,5aS)-5-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethylhexa hydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b-yl)methanol

The title compound was prepared by an analogous reaction protocol asdescribed in WO2006/091905 A1.

((3aR,3bR,4aS,5R,5aS)-5-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b-yl)methyl4-methyl benzenesulfonate

To a stirred solution of((3aR,3bR,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)methanol(2 g, 5.96 mmol) in CH₂Cl₂ (40 ml) at 0° C., was added TEA (2.494 ml,17.87 mmol), DMAP (0.146 g, 1.191 mmol) and followed by p-TsCl (1.363 g,7.15 mmol) slowly and stirred for 10 min. The reaction mixture wasstirred at 25° C. for 16 h. The reaction mixture was diluted withmethylene chloride (100 ml) and washed with water (100 ml). Layers wereseparated, organic layer was washed with brine (100 ml) and dried overanhydrous Na₂SO₄. The organic layer was filtered and concentrated invacuo to give 12 g of crude compound. This residue was purified bycombiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0 to 7%) of ethyl acetate in petroleumether to afford the title (0.267 g, 9.15%) as an off-white solid. LCMSm/z=490.17 (M+, 100%).

(3aR,3bS,4aS,5R,5aS)-5-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b-carbaldehyde

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.¹H NMR (400 MHz, Chloroform-d) δ 9.34 (s, 1H), 8.63 (s, 1H), 7.18 (d,J=3.6 Hz, 1H), 6.66 (d, J=3.6 Hz, 1H), 5.91 (dd, J=7.1, 1.2 Hz, 1H),5.11 (s, 1H), 4.82 (dd, J=7.1, 1.6 Hz, 1H), 2.34 (ddd, J=9.4, 6.1, 1.6Hz, 1H), 1.89-1.77 (m, 2H), 1.58 (s, 3H), 1.30 (s, 3H); LCMS m/z=333.9(M+, 100%).

4-Chloro-7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydrocyclopropa [3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine

To a stirred suspension of methyltriphenylphosphonium bromide (24.62 g,68.9 mmol) in THF (200 ml), was added 1M KHMDS in THF (68.9 ml, 68.9mmol) at 25° C. and stirred for 10 min. The resulting yellow suspensionwas cooled to 0° C. and a solution of (3aR,3bS,4aS,5R,5aS)-5-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b-carbaldehyde (9.2 g, 27.6 mmol) inTHF (80 ml) was added slowly. The reaction mixture was stirred at thesame temperature for 1 h. The reaction mixture was quenched with asaturated aq.NH₄Cl (200 ml) and extracted with ethyl acetate (200 ml).Layers were separated, organic layer was washed with brine (250 ml) anddried over anhydrous Na₂SO₄. The organic layer was filtered andconcentrated in vacuo to give 11 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0 to 20%) of ethyl acetatein petroleum ether to afford the title compound (7 g, 77%) as a whitesolid. ¹H NMR (400 MHz, Chloroform-d) δ 8.68 (s, 1H), 7.23 (d, J=3.7 Hz,1H), 6.67 (d, J=3.6 Hz, 1H), 5.86 (dd, J=17.3, 10.6 Hz, 1H), 5.39-5.32(m, 2H), 5.29 (s, 1H), 5.18 (dd, J=10.6, 0.9 Hz, 1H), 4.59 (dd, J=7.1,1.6 Hz, 1H), 1.77 (ddd, J=9.3, 4.9, 1.6 Hz, 1H), 1.63 (s, 3H), 1.49 (t,J=5.3 Hz, 1H), 1.27 (s, 3H), 1.18 (ddd, J=9.3, 5.6, 1.6 Hz, 1H); LCMSm/z=332.28 (M+, 50%).

7-((3aR,3bS,4aS,5R,5aS)-2,2-Dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

A mixture of4-chloro-7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydrocyclopropa [3,4] cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (3 g, 9.04mmol) and aq. ammonia (19.57 ml, 904 mmol) in dioxane (6 ml) stirred at130° C. in a steel bomb for 16 h. The reaction mixture was diluted withethyl acetate (20 ml) and washed with water (20 ml). Layers wereseparated, organic layer was washed with brine (20 ml) and dried overanhydrous Na₂SO₄. The organic layer was filtered and concentrated invacuo to give 4.1 g of crude compound. This residue was purified bycombiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0 to 3%) of methanol in dichloromethane toafford the title compound (2.45 g, 87%) as a white solid. ¹H NMR (400MHz, DMSO-d₆) δ 8.07 (s, 1H), 7.02 (s, 2H), 6.96 (d, J=3.5 Hz, 1H), 6.62(d, J=3.5 Hz, 1H), 5.86 (dd, J=17.4, 10.7 Hz, 1H), 5.33 (dd, J=7.2, 1.3Hz, 1H), 5.23 (dd, J=17.4, 1.3 Hz, 1H), 5.10-5.01 (m, 2H), 4.50 (dd,J=7.1, 1.6 Hz, 1H), 1.70 (ddd, J=9.3, 4.8, 1.6 Hz, 1H), 1.46 (s, 3H),1.29-1.22 (m, 1H), 1.19 (s, 3H), 1.10 (ddd, J=9.1, 5.1, 1.5 Hz, 1H);LCMS m/z=313 (M+1, 100%).

7-((3aR,3bS,4aS,5R,5aS)-2,2-Dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidine

To a degassed mixture dioxane (8 ml) and water (1 ml) in a microwavevial was added4-chloro-7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (1.00 g, 3.01 mmol,potassium phosphate, tribasic (1.575 g, 9.04 mmol),dichloro[1,1′-bis(di-t-butylphosphino)ferrocene] palladium(II) (0.196 g,0.301 mmol) and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (2.107 ml,15.07 mmol) at 25° C. Stirred the reaction mixture at 100° C. for 1 h.The reaction mixture was diluted with ethyl acetate (20 ml) and washedwith water (20 ml). Layers were separated, organic layer was washed withbrine (20 ml) and dried over anhydrous Na₂SO₄. The organic layer wasfiltered and concentrated in vacuo to give 1.1 g of crude compound. Thisresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution (0 to 20%) of ethylacetate in petroleum ether to afford the title compound (0.66 g, 70.3%)as an off white solid. ¹H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 1H),7.16 (d, J=3.6 Hz, 1H), 6.63 (d, J=3.6 Hz, 1H), 5.87 (dd, J=17.3, 10.6Hz, 1H), 5.37-5.31 (m, 3H), 5.17 (dd, J=10.6, 0.9 Hz, 1H), 4.58 (dd,J=7.1, 1.6 Hz, 1H), 2.78 (s, 3H), 1.78 (ddt, J=9.3, 4.9, 1.8 Hz, 1H),1.59 (d, J=1.8 Hz, 3H), 1.50 (td, J=5.2, 2.7 Hz, 1H), 1.27 (d, J=2.2 Hz,3H), 1.19-1.14 (m, 1H); LCMS m/z=312.21 (M+1, 100%).

Des chloro compound i.e.7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydro cyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidinewas also formed, which was separated at final step by reverse phasepreparative HPLC.

(S)-1-((3aR,3bR,4aS,5R,5aS)-5-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethan-1-ol

To a solution of(3aR,3bS,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carbaldehyde(2.0 g, 5.99 mmol) in tetrahydrofuran (20 ml), was added 1M methylmagnesium bromide in THF (3.00 ml, 8.99 mmol) at 0° C. The reactionmixture was then stirred at 0° C. for 2 h. The reaction mixture wasquenched with a sat. aq. ammonium chloride (50 ml) and extracted withethyl acetate (50 ml×2). The combined organic layer was washed withbrine (50 ml), dried over sodium sulfate, filtered and concentrated invacuo to give 2.2 g of crude compound. This residue was purified bycombiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0 to 30%) of ethyl acetate in petroleumether to afford the title compound (1.85 g, 88%) as an off-white solid.LCMS m/z=350.03 (M+1; 100%).

1-((3aR,3bS,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethan-1-one

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.LCMS m/z=348.03 (M+; 100%).

4-Chloro-7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine

To a stirred suspension of methyltriphenylphosphonium bromide (3.85 g,10.78 mmol) in THF (40 ml) was added 1M KHMDS in THF (10.78 ml, 10.78mmol) at 0° C. and stirred for 10 min. To this yellow suspension wasadded a solution of1-((3aR,3bS,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetra hydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethan-1-one (1.5 g, 4.31mmol) in THF (20 ml) was added slowly at 0° C. The reaction mixture wasstirred at 25° C. for 1 h. The reaction mixture was quenched with asaturated aqueous ammonium chloride (50 ml) and extracted with ethylacetate (50 ml). Layers were separated, organic layer was washed withbrine (50 ml) and dried over anhydrous sodium sulphate. The organiclayer was filtered and concentrated in vacuo to give 2.2 g of crudecompound. This residue was purified by combiflash (R_(f)200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0 to 20%) of ethyl acetate in petroleum ether to afford thetitle compound (0.7 g, 46.9%) as a white solid. LCMS m/z=346.03 (M+1;100%).

(R)-((3aR,3bR,4aS,5R,5aS)-5-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)(cyclopropyl)methanol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(S)-1-((3aR,3bR,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethan-1-ol.LCMS m/z=375.91 (M+; 100%).

((3aR,3bS,4aS,5R,5aS)-5-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetra hydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)(cyclopropyl) methanone

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of1-((3aR,3bS,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethan-1-one.¹H NMR (400 MHz, DMSO-d6) δ 8.58 (s, 1H), 7.71 (d, J=3.7 Hz, 1H), 6.72(d, J=3.6 Hz, 1H), 5.84 (dd, J=7.3, 1.2 Hz, 1H), 5.21 (s, 1H), 4.79 (dd,J=7.3, 1.5 Hz, 1H), 2.09 (s, 1H), 2.07-2.01 (m, 1H), 1.79 (ddd, J=9.5,5.3, 1.4 Hz, 1H), 1.51 (t, J=5.5 Hz, 1H), 1.48 (s, 3H), 1.21 (s, 3H),0.96-0.74 (m, 4H); LCMS m/z=373.97 (M+; 100%).

4-Chloro-7-((3aR,3bR,4aS,5R,5aS)-3b-(1-cyclopropylvinyl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR(400 MHz, Chloroform-d) δ 8.67 (s, 1H), 7.29 (d, J=3.6 Hz, 1H), 6.68 (d,J=3.6 Hz, 1H), 5.37-5.35 (m, 2H), 4.98 (d, J=0.8 Hz, 1H), 4.80 (s, 1H),4.59 (dd, J=7.5, 1.6 Hz, 1H), 2.04 (ddd, J=9.3, 4.7, 1.6 Hz, 1H), 1.67(s, 2H), 1.42 (t, J=5.1 Hz, 1H), 1.27 (s, 6H), 0.75-0.69 (m, 2H),0.56-0.52 (m, 2H); LCMS m/z=372.2 (M+; 100%).

4-Chloro-7-((3aR,3bR,4aS,5R,5aS)-3b-((E)-2-iodoprop-1-en-1-yl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine

To a suspension of (1-iodoethyl)triphenylphosphonium bromide (4.08 g,7.49 mmol, synthesized by following same reaction protocol as wasdescribed in WO2004/9574, A1) in THF (20 ml)), was added NaHMDS (7.49ml, 7.49 mmol) at −25° C. The resulting red coloured solution wasstirred at −25° C. for 10 min. A solution of(3aR,3bS,4aS,5R,5aS)-5-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta [1,2-d][1,3]dioxole-3b(3aH)-carbaldehyde (1.00g, 3.00 mmol) in THF (20 ml) was added at −30° C. and stirred for 30mins. The reaction mixture was quenched with sat aq.NH₄Cl (20 ml) andextracted with ethyl acetate (20 ml). Layers were separated, organiclayer was washed with brine (20 ml) and dried over anhydrous Na₂SO₄. Theorganic layer was filtered and concentrated in vacuo to give 1.04 g ofcrude compound. This residue was purified by combiflash (R_(f)200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0 to 10%) of ethyl acetate in petroleum ether to afford thetitle compound (0.79 g, 55.9%) as an off-white solid. LCMS m/z=471.80(M+; 100%).

7-((3aR,3bR,4aS,5R,5aS)-3b-(((tert-Butyldiphenylsilyl)oxy)methyl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-4-chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of1-((3aS,4R,6aR)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-4-chloro-1H-pyrrolo[3,2-c]pyridine. LCMS m/z=587.82 (M+; 100%).

((3aR,3bR,4aS,5R,5aS)-5-(4-Chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)methanol

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of((3aR,6R,6aS)-6-(2-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol.¹H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 6.48 (d, J=1.1 Hz, 1H),5.34-5.25 (m, 1H), 4.98 (s, 1H), 4.90 (dt, J=7.4, 1.3 Hz, 1H), 4.66 (t,J=5.7 Hz, 1H), 3.65 (q, J=5.8, 5.3 Hz, 2H), 2.57 (s, 3H), 1.54-1.48 (m,1H), 1.46 (s, 3H), 1.19 (s, 3H), 0.92 (ddd, J=9.0, 5.0, 1.3 Hz, 1H),0.85 (q, J=4.7, 4.3 Hz, 1H); LCMS m/z=350.03 (M+; 100%).

(3aR,3bS,4aS,5R,5aS)-5-(4-Chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carbaldehyde

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of(3aS,4R,6aR)-2,2-dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde.LCMS m/z=348.03 (M+; 100%).

4-Chloro-7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-6-methyl-7H-pyrrolo[2,3-d]pyrimidine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of4-chloro-7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydrocyclopropa [3,4] cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine. ¹H NMR (400MHz, Chloroform-d) δ 8.57 (s, 1H), 6.38 (q, J=1.1 Hz, 1H), 5.88 (dd,J=17.3, 10.6 Hz, 1H), 5.64 (dd, J=7.2, 1.4 Hz, 1H), 5.34-5.23 (m, 1H),5.10 (dd, J=10.6, 1.1 Hz, 1H), 5.02-4.96 (m, 1H), 4.87 (s, 1H), 2.55 (s,3H), 1.59 (s, 3H), 1.56-1.51 (m, 1H), 1.30 (s, 3H), 1.29-1.26 (m, 1H),1.19-1.12 (m, 1H); LCMS m/z=346.03 (M+; 100%).

7-((3aR,3bS,4aS,5R,5aS)-2,2-Dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclo penta[1,2-d][1,3]dioxol-5-yl)-6-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

The title compound was synthesized by following an analogous reactionprotocol as was described in the preparation of7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexa hydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine. ¹H NMR (400MHz, DMSO-d6) δ 7.99 (s, 1H), 6.83 (s, 2H), 6.29 (d, J=1.2 Hz, 1H),5.87-5.74 (m, 2H), 5.44 (d, J=7.3 Hz, 1H), 5.19 (dd, J=17.4, 1.4 Hz,1H), 5.02 (dd, J=10.7, 1.3 Hz, 1H), 4.80 (d, J=7.3 Hz, 1H), 2.36 (s,3H), 1.61 (dd, J=9.0, 5.3 Hz, 1H), 1.46 (s, 3H), 1.21 (s, 3H), 1.15-1.08(m, 2H); LCMS m/z=327.1 (M+1; 100%).

3-Bromo-7-(2-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxo-6-yl)ethyl)-N-(4-methoxybenzyl)quinolin-2-amine

4-Chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine (0.25 g, 0.787mmol) in 9-BBN (0.5 molar, 6.29 ml, 3.15 mmol) was heated at 70° C. for2 h under N₂ atmosphere. The reaction mixture was cooled to 25° C., thenpotassium phosphate tribasic (0.685 g, 3.93 mmol) in water (0.5 ml) wasadded and stirred for 20 mins. A solution of3-bromo-7-iodo-N-(4-methoxybenzyl)quinolin-2-amine (0.369 g, 0.787 mmol)in THF (1 ml) was added, followed by PdCl₂(dppf) (0.058 g, 0.079 mmol).The resulting mixture was stirred at 70° C. for 2 h. The reactionmixture was diluted with ethyl acetate (10 ml) and washed with water (10ml). Layers were separated, organic layer was washed with brine (10 ml)and dried over anhydrous Na₂SO₄. The organic layer was filtered andconcentrated in vacuo to give 0.35 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0 to 15%) of ethyl acetatein petroleum ether to afford the title compound (0.25 g, 48.1%) as anoff-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 8.37 (s, 1H),7.60 (d, J=8.2 Hz, 1H), 7.45 (s, 1H), 7.33 (d, J=8.5 Hz, 2H), 7.28-7.14(m, 2H), 6.98 (d, J=3.7 Hz, 1H), 6.87-6.75 (m, 2H), 6.36 (d, J=3.6 Hz,1H), 5.66 (s, 1H), 5.52 (s, 1H), 5.35 (d, J=5.7 Hz, 1H), 4.63 (d, J=6.0Hz, 2H), 4.49 (d, J=5.7 Hz, 1H), 3.66 (s, 3H), 3.07-2.97 (m, 2H),2.65-2.59 (m, 2H), 1.39 (s, 3H), 1.28 (s, 3H). LCMS m/z=658.89, 661.64(M−2, M+1, 100%).

Intermediates in table-5 were synthesized by an analogous reactionprotocol as was used for the preparation of3-bromo-7-(2-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethyl)-N-(4-methoxybenzyl)quinolin-2-amine using the appropriate starting materials.

TABLE 5 ¹H NMR & LCMS Structure & IUPAC name- Intermediates used data

7-Bromo-N-methyl quinolin-2- amine and 4-Chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl- 3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-4-yl)- 7H-pyrrolo[2,3-d]pyrimidine LCMS m/z = 476.05 (M+, 100%)

4-Chloro-7-((3aS,4R,6aR)-2,2- dimethyl-6-vinyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol- 4-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine and 3-Bromo-7- iodo-N-(4- methoxybenzyl)quinolin-2- amineLCMS m/z = 679.85 (M + 1, 100%)

7-Bromo-3-fluoro quinolin-2- amine and 4-Chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl- 3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-4-yl)- 7H-pyrrolo[2,3-d]pyrimidine ¹H NMR (400 MHz, DMSO-d₆) δ8.65 (s, 1H), 7.81 (d, J = 11.9 Hz, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.41(d, J = 1.6 Hz, 1H), 7.19 (dd, J = 8.2, 1.6 Hz, 1H), 6.95 (d, J = 3.7Hz, 1H), 6.84-6.67 (m, 2H), 6.41 (d, J = 3.7 Hz, 1H), 5.66 (s, 1H), 5.52(s, 1H), 5.34 (d, J = 5.7 Hz, 1H), 4.51 (dd, J = 15.1, 5.6 Hz, 1H),3.18- 2.98 (m, 2H), 2.80- 2.56 (m, 2H), 1.39 (s, 3H), 1.28 (s,, 3H).LCMS m/z = 480.2 (M+, 100%)

4-Chloro-7-((3aS,4R,6aR)-2,2- dimethyl-6-(prop-1-en-2-yl)-3a,6a-dihydro-4H-cyclopenta[d] [1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine and 3- Bromo-7-iodo-N-(4-methoxybenzyl)quinolin-2- amine LCMS m/z = 676.47 (M + 1, 100%)

4-Chloro-7-((3aS,4R,6aR)-2,2- dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-7H-pyrrolo[2,3- d]pyrimidineand 7-Bromo-N- cyclobutylquinolin-2-amine ¹H NMR (400 MHz, Chloroform-d)δ 8.65 (s, 1H), 7.89 (d, J = 8.9 Hz, 1H), 7.60-7.51 (m, 2H), 7.16 (dd, J= 8.1, 1.7 Hz, 1H), 6.65 (d, J = 8.9 Hz, 1H), 6.46 (d, J = 3.7 Hz, 1H),6.25 (d, J = 3.7 Hz, 1H), 5.77 (s, 1H), 5.44 (t, J = 1.7 Hz, 1H),5.32-5.28 (m, 2H). 4.48-4.41 (m, 2H), 3.22-3.02 (m, 2H), 2.83-2.77 (m,2H), 2.58-2.46 (m, 2H). 2.07-1.96 (m, 2H), 1.85 (ddd, J = 10.6, 9.0, 6.4Hz, 2H), 1.51 (s, 3H), 1.38 (s, 3H); LCMS m/z = 515.19 (M − l, 100%)

7-((3aS,4R,6aR)-2,2-dimethyl- 6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)- 4-methyl-7H-pyrrolo[2,3-d] pyrimidine &7-bromo-3-chloro quinolin-2-amine LCMS m/z = 476.36 (M+, 60%)

4-Chloro-7-((3aS,4R,6aR)-2,2- dimethyl-6-(prop-1-en-2-yl)-3a,6a-dihydro-4H-cyclopenta [d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine & 7- bromo-3-chloro quinolin-2- amine LCMS m/z= 510.2 (M+, 100%)

¹H NMR (400 MHz, Chloroform-d) δ 8.76- 8.62 (m, 2H), 7.76 (s, 1H), 7.25(dd, J = 10.4, 1.5 Hz, 1H), 6.84 (d, J = 3.7 Hz, 1H), 6.54 (d, J = 3.6Hz, 1H), 5.81 (s, 1H), 5.55 (s, 1H), 5.37-5.29 (m, 1H), 4.58 (d, J = 5.7Hz, 1H), 3.25- 3.12 (m, 2H), 2.89- 2.72 (m, 2H), 1.51 (s, 3H), 1.45 (s,9H), 1.43 (s, 9H), 1.38 (s, 3H); LCMS m/z = 760.41 (M + 1, 40%).

¹H NMR (400 MHz, DMSO-d₆) δ 8.88 (s, 1H), 8.64 (s, 1H), 7.85 (s, 1H),7.63 (dd, J = 11.0, 1.5 Hz, 1H), 6.80 (d, J = 3.6 Hz, 1H), 6.48 (d, J =3.7 Hz, 1H), 5.65 (s, 1H), 5.56 (s, 1H), 5.37 (d, J = 5.6 Hz, 1H), 4.44(d, J = 5.7 Hz, 1H), 3.22-3.13 (m, 2H), 2.78-2.66 (m, 2H), 2.61 (s, 3H),1.38 (s, 9H), 1.35 (s, 3H), 1.33 (s, 9H), 1.27 (s, 3H); LCMS m/z =738.61 (M+, 90%), 740.61 (M + 2, 100%).

LCMS m/z = 796.20 (M + 23, 60%).

4-Chloro-1-((3aS,4R, 6aR)-2,2- dimethyl-6-vinyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol- 4-yl)-1H-pyrrolo[3,2-c] pyridine &7-Bromo-3- methylimidazo[1,2-a]pyridine LCMS m/z = 450.04 (M+, 100%)

3-Chloro-7-(2-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethyl)-5-fluoroquinolin-2-amine

4-Chloro-7-((3aS,4R,6aR)-2,2-dimethyl-6-vinyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine(0.242 g, 0.762 mmol) in 9-BBN (0.5 molar, 4.36 ml,

2.178 mmol) was heated at 50° C. for 1 h under N₂ atmosphere. Thereaction mixture was cooled to 25° C., then potassium phosphate tribasic(0.578 g, 2.72 mmol) in water (0.5 ml) was added and stirred for 20mins. A solution of 7-bromo-3-chloro-5-fluoroquinolin-2-amine (0.150 g,0.544 mmol) in THF (0.5 ml) was added, followed bydichloro[1,1′-bis(di-t-butylphosphino)ferrocene]palladium(II) (0.035 g,0.054 mmol). The resulting mixture was stirred at 50° C. for 6 h. Thereaction mixture was diluted with water (10 ml) and extracted with ethylacetate (10 ml). Layers were separated, organic layer was washed withbrine (10 ml) and dried over anhydrous Na₂SO₄. The organic layer wasfiltered and concentrated in vacuo to give 0.345 g of crude compound.This residue was purified by combiflash (R_(f)200, Teledyne/Isco)instrument onto a Redisep® R_(f) column with gradient elution (0 to 35%)of ethyl acetate in petroleum ether to afford the title compound (0.16g, 57.5%) as an off-white solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.64 (s,1H), 8.18 (s, 1H), 7.25 (s, 1H), 7.09-6.96 (m, 4H), 6.44 (d, J=3.6 Hz,1H), 5.67 (s, 1H), 5.56-5.51 (m, 1H), 5.35 (d, J=5.7 Hz, 1H), 4.52 (d,J=5.7 Hz, 1H), 3.05-2.98 (m, 2H), 2.74-2.56 (m, 2H), 1.38 (s, 3H), 1.28(s, 3H); LCMS m/z=514.2 (M+, 100%).

Intermediates in table-6 were synthesized by an analogous reactionprotocol as was used for the preparation of3-chloro-7-(2-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethyl)-5-fluoroquinolin-2-amineusing the appropriate starting materials.

TABLE 6 Structure & IUPAC name Intermediates used ¹H NMR & LCMS data

4-Chloro-7-((3aS,4R. 6aR)-2,2-dimethyl-6- vinyl-3a,6a-dihydro-4H-cyclopenta [d][1,3]dioxol-4-yl)- 7H-pyrrolo[2,3-d] pyrimidine and 7-Bromo-3-chloro-6- fluoroquinolin-2- amine ¹H NMR (400 MHz, DMSO-d6) δ8.65 (s, 1H), 8.18 (s, 1H), 7.56-7.44 (m, 2H), 7.14 (d, J = 3.7 Hz, 1H),6.73 (s, 2H), 6.50 (d, J = 3.7 Hz, 1H), 5.69 (s, 1H), 5.60-5.52 (m, 1H),5.42- 5.31 (m, 1H), 4.53 (dd, J = 5.7, 2.8 Hz, 1H), 3.08-3.01 (m, 2H),2.66-2.62 (m, 2H), 1.39 (s, 3H), 1.28 (s, 3H); LCMS m/z = 515 (M + 1,100%).

4-Chloro-7-((3aS,4R, 6aR)-2,2-dimethyl-6- vinyl-3a,6a-dihydro-4H-cyclopenta[d] [1,3]dioxol-4-yl)-7H- pyrrolo[2,3-d] pyrimidine and 7-Bromo-3- chloroquinolin-2- amine ¹H NMR (400 MHz, DMSO-d6) δ 8.65 (s,1H), 8.19 (s, 1H), 7.61 (d, J = 8.2 Hz, 1H), 7.40 (s, 1H), 7.19 (dd, J =8.1, 1.7 Hz, 1H), 6.96 (d, J = 3.6 Hz, 1H), 6.72 (s, 2H), 6.41 (d, J =3.6 Hz, 1H), 5.66 (s, 1H), 5.52 (s, 1H), 5.34 (d, J = 5.7 Hz, 1H), 4.49(d, J = 5.6 Hz, 1H), 3.10- 2.96 (m, 2H), 2.79-2.60 (m, 2H), 1.38 (s,3H), 1.28 (s, 3H); LCMS m/z = 496.05 (M+, 100%)

4-Chloro-7- ((3aS,4R,6aR)-2,2- dimethyl-6-(prop-1- en-2-yl)-3a,6a-dihydro-4H- cyclopcnta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3-d]pyrimidine and 7- Bromo-3-chloro-5- fluoroquinolin-2- amine ¹H NMR(400 MHz, DMSO-d₆) δ 8.64 (d, J = 6.1 Hz, 1H), 8.22-8.16 (m, 1H),7.29-7.14 (m, 2H), 7.00-6.95 (m, 3H), 6.56 (d, J = 3.6 Hz, 1H), 5.67 (d,J = 14.7 Hz, 1H), 5.57 (s, 1H), 5.40-5.34 (m, 1H), 4.54 (dd, J = 15.1,5.7 Hz, 1H), 3.04 (q, J = 9.6, 7.8 Hz, 1H), 2.87 (s, 2H), 1.30 (d, J =9.7 Hz, 3H), 1.19 (d, 6H); LCMS m/z = 528.32 (M+, 100%)

7-((3aS,4R,6aR)-2,2- Dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-4-methyl- 7H-pyrrolo[2,3- d]pyrimidineand 7- Bromo-3-chloro-5- fluoroquinolin-2- amine ¹H NMR (400 MHz.Chloroform-d) δ 8.83 (s, 1H), 8.22 (d, J = 0.8 Hz, 1H), 7.34 (s, 1H),6.92 (dd, J = 10.6, 1.5 Hz, 1H), 6.68 (d, J = 3.6 Hz, 1H), 6.38 (d, J =3.6 Hz, 1H), 5.80 (s, 1H), 5.52-5.47 (m, 2H), 4.55 (d, J = 5.7 Hz, 1H),3.12-3.06 (m, 2H), 2.77-2.74 (m, 2H), 2.74 (s, 3H), 1.51 (s, 3H), 1.38(s, 3H); LCMS m/z = 494.3 (M+, 80%)

2-Chloro-7- ((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 4,6a-dihydro-3aH-cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3- d]pyrimidine and 7-Bromo-3- chloroquinolin-2- amine ¹H NMR (400 MHz, Chloroform-d) δ 8.76(s, 1H), 7.98 (s, 1H), 7.55 (d, J = 8.2 Hz, 2H), 7.22 (dd, J = 8.1, 1.7Hz, 1H), 6.52 (d, J = 3.6 Hz, 1H), 6.28 (d, J = 3.7 Hz, 1H), 5.75 (s,1H), 5.42 (d, J = 2.4 Hz, 1H), 5.34 (d, J = 10.9 Hz, 3H), 4.52 (d, J =5.6 Hz, 1H), 3.18-3.07 (m, 2H), 2.81-2.76 (m, 2H), 1.49 (s, 3H), 1.38(s, 3H); LCMS m/z = 496.24 (M+, 60%)

7-((3aS,4R,6aR)-2,2- Dimethyl-6-(prop-1- en-2-yl)-4,6a-dihydro-3aH-cyclopenta[d] [1,3]dioxol-4-yl)-4- methyl-7H-pyrrolo[2,3-d]pyrimidine and 7-Bromo-3-chloro-5- fluoroquinolin-2- amine LCMSm/z = 508.31 (M+, 100%)

7-((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3- d]pyrimidine and 7-Bromo-3-chloro-5- fluoroquinolin-2- amine ¹H NMR (400 MHz, Chloroform-d)δ 8.93 (d, J = 10.4 Hz, 2H), 8.24 (s, 1H), 7.37 (s, 1H), 6.94 (dd, J =10.8, 1.4 Hz, 1H), 6.71 (d, J = 3.6 Hz, 1H), 6.37 (d, J = 3.6 Hz, 1H),5.83 (s, 1H), 5.72 (s, 2H), 5.50 (s, 1H), 5.31 (d, J = 5.7 Hz, 1H), 4.56(d, J = 5.7 Hz, 1H), 3.16- 3.04 (m, 2H), 2.78-2.76 (m, 2H), 1.52 (s,3H), 1.38 (s, 3H); LCMS m/z = 480.2 (M+, 70%)

7-((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-4-isopropyl- 7H-pyrrolo[2,3-d]pyrimidine & 7- Bromo-3-chloro-5- fluoroquinolin-2- amine LCMS m/z =522.32 (M+, 100%)

7-((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-4-ethyl-7H- pyrrolo[2,3- d]pyrimidine &7- Bromo-3-chloro-5- fluoroquinolin-2- amine ¹H NMR (400 MHz, DMSO-d6) δ8.68 (s, 1H), 8.18 (s, 1H), 7.25 (s, 1H), 7.05 (dd, J = 11.0, 1.4 Hz,1H), 6.96 (s, 2H), 6.85 (d, J = 3.6 Hz, 1H), 6.49 (d, J = 3.6 Hz, 1H),5.66 (s, 1H), 5.52 (s, 1H), 5.34 (d, J = 5.7 Hz, 1H), 4.46 (d, J = 5.6Hz, 1H), 3.05-2.93 (m, 4H), 2.66-2.59 (m, 2H), 1.38 (s, 3H), 1.31-1.24(m, 6H); LCMS m/z = 508.31 (M+, 100%)

7-((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-4-(1-methyl- 1H-pyrazol-4-yl)-7H-pyrrolo[2,3- d]pyrimidine & 7- Bromo-3-chloro-5- fluoroquinolin-2- amine¹H NMR (400 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.60 (s, 1H), 8.23 (s, 1H),8.19 (s, 1H), 7.27 (s, 1H), 7.10-6.95 (m, 4H), 6.79 (d, J = 3.7 Hz, 1H),5.70 (s, 1H), 5.55 (s, 1H), 5.36 (d, J = 5.6 Hz, 1H), 4.50 (d, J = 5.7Hz, 1H), 3.97 (s, 3H), 3.10- 2.94 (m, 2H), 2.71-2.60 (m, 2H), 1.39 (s,3H), 1.29 (s, 3H); LCMS m/z = 560.33 (M+, 100%)

4-chloro-7- ((3aS,4R.6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3- d]pyrimidine & 7-Bromo-3-chloro-8- fluoroquinolin-2- amine ¹H NMR (400 MHz, DMSO-d₆) δ8.65 (s, 1H), 8.26 (d, J = 1.6 Hz, 1H), 7.62 (s, 1H), 7.45 (d, J = 8.3Hz, 1H), 7.27-7.15 (m, 1H), 7.03 (s, 2H), 6.51 (d, J = 3.7 Hz, 1H), 5.69(s, 1H), 5.55 (s, 1H), 5.36 (d, J = 5.7 Hz, 1H), 4.54 (d, J = 5.7 Hz,1H), 3.12-3.0 (m, 2H), 2.66- 2.58 (m, 2H), 1.29 (s, 3H), 1.24 (s, 3H);LCMS m/z = 515.57 (M + 1, 40%)

4-chloro-7- ((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3- d]pyrimidine & 6-Bromo-3,3-dimethyl- 2-(methylthio)-3H- indole ¹H NMR (400 MHz, DMSO-d₆)δ 8.67 (s, 1H), 7.42-7.28 (m, 2H), 7.17- 6.99 (m, 2H), 6.51 (d, J = 3.6Hz, 1H), 5.68 (s, 1H), 5.53 (s, 1H), 5.36 (d, J = 5.7 Hz, 1H), 4.52 (d,J = 5.6 Hz, 1H), 3.07-2.85 (m, 2H), 2.71-2.56 (m, 5H), 1.38 (s, 3H),1.29 (d, J = 3.4 Hz, 9H); LCMS m/z = 510.31 (M + 1, 60%)

4-Chloro-1- ((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 4,6a-dihydro-3aH-cyclopenta[d][1,3] dioxol-4-yl)-1H- pyrrolo[3,2-c]pyridine &6′-Bromo-2′-(methylthio)spiro [cyclobutane-1,3′-indole] ¹H NMR (400 MHz, DMSO-d₆) δ8.66 (s, 1H), 7.61 (d, J = 7.5 Hz, 1H), 7.31 (d, J = 1.4 Hz, 1H), 7.09(dd, J = 7.6, 1.5 Hz, 1H), 7.01 (d, J = 3.7 Hz, 1H), 6.46 (d, J = 3.6Hz, 1H), 5.67 (s, 1H), 5.53 (s, 1H), 5.35 (d, J = 5.6 Hz, 1H), 4.52 (d,J = 5.6 Hz, 1H), 3.02-2.86 (m, 2H), 2.69-2.56 (m, 5H), 2.48- 2.39 (m,4H), 2.39-2.18 (m, 2H), 1.39 (s, 3H), 1.29 (s, 3H); LCMS m/z = 521.19(M+, 30%)

4-methyl-7- ((3aS,4R,6aR)-2,2,6a- trimethyl-6-(prop-1- en-2-yl)-3a,6a-dihydro-4H- cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3-d]pyrimidine and 7- bromo-3-chloro-5- fluoroquinolin-2- amine LCMS m/z =522.32 (M+, 100%)

4-Cyclopropyl-7- ((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3- d]pyrimidine and 7-Bromo-3-chloro-5- fluoroquinolin-2- amine LCMS m/z = 520.14 (M+, 100%)

4-Chloro-7- ((3aS,4R,6aR)-2,2,6a- trimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d] [1,3]dioxol-4-yl)-7H- pyrrolo[2,3- d]pyrimidine &7-Bromo-3-chloro- 5-fluoroquinolin-2- amine ¹H NMR (400 MHz,Chloroform-d) δ 8.72 (s, 1H), 8.22 (d, J = 0.8 Hz, 1H), 7.37 (s, 1H),6.99 (d, J = 3.6 Hz, 1H), 6.96-6.89 (m, 1H), 6.55 (d, J = 3.7 Hz, 1H),5.76 (s, 1H), 5.58- 5.46 (m, 3H), 4.18-4.13 (m, 1H), 3.20-3.05 (m, 2H),2.77-2.62 (m, 2H), 1.50 (s, 3H), 1.44 (s, 3H), 1.42 (s, 3H); LCMS m/z =528.19 (M+, 100%)

4-Methyl-7- ((3aS,4R,6aR)-2,2,6a- trimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3- d]pyrimidine & 7-Bromo-3-chloro-5- fluoroquinolin-2- amine ¹H NMR (400 MHz, DMSO-d₆) δ8.68 (s, 1H), 8.18 (s, 1H), 7.27 (s, 1H), 7.12-7.03 (m, 2H), 6.96 (s,2H), 6.66-6.51 (m, 1H), 5.64 (s, 1H), 5.58 (s, 1H), 4.04 (s, 1H),3.14-3.02 (m, 2H), 2.74-2.59 (m, 5H), 1.39 (s, 3H), 1.30 (d, J = 3.5 Hz,6H); LCMS m/z = 508.31 (M+, 100%)

4-chloro-7- ((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3- d]pyrimidine & 3,5-Dichloro-7-iodoquinolin- 2-amine LCMS m/z = 532.19 (M + 1, 90%)

4-chloro-7- ((3aS,4R.6aR)-2,2,6a- trimethyl-6-(prop-1- en-2-yl)-3a,6a-dihydro-4H- cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3-d]pyrimidine & 7- bromo-3-chloro-5- fluoroquinolin-2- amine ¹H NMR (400MHz, DMSO-d₆) δ 8.66 (s, 1H), 8.14 (s, 1H), 7.25 (s, 1H), 7.07 (dd, J =11.1, 1.3 Hz, 1H), 7.01 (s, 2H), 6.69 (d, J = 3.7 Hz, 1H), 6.35 (d, J =3.7 Hz, 1H), 5.77 (d, J = 2.7 Hz, 1H), 5.60 (d, J = 2.7 Hz, 1H), 4.01(s, 1H), 3.10- 2.93 (m, 2H), 2.92-2.80 (m, 1H), 1.37 (s, 3H), 1.27 (s,3H), 1.25 (d, J = 6.0 Hz, 3H), 1.11 (s, 3H), LCMS m/z = 542.20 (M+,100%)

1-((3aS,4R,6aR)-2,2- Dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-4-methyl- 1H-pyrrolo[3,2- c]pyridine, 1-((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-1H- pyrrolo[3,2-c]pyridine and7-bromo-3- chloro-5- fluoroquinolin-2- amine LCMS m/z = 493.36 (M+,100%)

1-((3aS,4R,6aR)-2,2- Dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-4-methyl- 1H-pyrrolo[3,2- c]pyridine, 1-((3aS,4R,6aR)-2,2- dimethyl-6-vinyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3] dioxol-4-yl)-1H- pyrrolo[3,2-c]pyridine and7-bromo-3- chloro-5- fluoroquinolin-2- amine LCMS m/z = 479.30 (M+,100%)

4-Chloro-7-((3aS,4R, 6aR)-6a-ethyl-2,2- dimethyl-6-vinyl-4,6a-dihydro-3aH- cyclopenta[d] [1,3]dioxol-4-yl)-7H- pyrrolo[2,3-d]pyrimidine & 7- Bromo-3-chloro-5- fluoroquinolin-2- amine ¹H NMR (400MHz, DMSO-d₆) δ 8.70 (s, 1H), 8.18 (s, 1H), 7.34 (d, J = 3.7 Hz, 1H),7.28 (s, 1H), 7.07 (dd, J = 11.1, 1.4 Hz, 1H), 6.96 (s, 2H), 6.60 (d, J= 3.7 Hz, 1H), 5.79 (s, 1H), 5.58 (d, J = 2.3 Hz, 1H), 4.23 (s, 1H),3.18-2.98 (m, 2H), 2.67-2.53 (m, 2H), 1.68- 1.52 (m, 2H), 1.31 (s, 3H),1.28 (s, 3H), 0.70-0.61 (m, 3H); LCMS m/z = 542.3 (M+, 100%)

4-methyl-7- ((3aS,4R,6aR)-2,2,6a- trimethyl-6-(prop-1- en-2-yl)-3a,6a-dihydro-4H- cyclopenta[d][1,3] dioxol-4-yl)-7H- pyrrolo[2,3-d]pyrimidine & 7-bromo-3-chloro-5- fluoroquinolin-2- amine LCMS m/z =522.32 (M+, 100%)

7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)-3-chloro-5-fluoroquinolin-2-amine

7-((3aR,3bS,4aS,5R,5aS)-2,2-Dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (1 g, 3.20 mmol) in 9-BBN (0.5 molar, 25.6 ml,12.81 mmol) was heated at 60° C. for 1 h under N2 atmosphere. Thereaction mixture was cooled to 25° C., then potassium phosphate tribasic(3.40 g, 16.01 mmol) in water (2 ml) was added and stirred for 30 mins.A solution of 7-bromo-3-chloro-5-fluoroquinolin-2-amine (0.882 g, 3.20mmol) in THF (12 ml) was added, followed by PdCl₂(dppf) (0.234 g, 0.320mmol). The resulting mixture was stirred at 50° C. for 6 h. The reactionmixture was diluted with water (10 ml) and extracted with ethyl acetate(10 ml). Layers were separated, organic layer was washed with brine (10ml) and dried over anhydrous Na₂SO₄. The organic layer was filtered andconcentrated in vacuo to give 1.5 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0 to 5%) of methanol indichloromethane to afford the title compound (1.3 g, 80%) as a paleyellow semisolid. ¹H NMR (400 MHz, DMSO-d₆) δ 8.16 (s, 1H), 8.08 (s,1H), 7.22 (s, 1H), 7.12 (d, J=3.5 Hz, 1H), 7.05 (d, J=1.4 Hz, 1H), 7.02(s, 2H), 6.94 (s, 2H), 6.61 (d, J=3.5 Hz, 1H), 5.20 (d, J=7.2 Hz, 1H),5.01 (s, 1H), 4.52 (dd, J=7.3, 1.5 Hz, 1H), 2.85-2.80 (m, 2H), 2.32-2.26(m, 1H), 1.72-1.56 (m, 1H), 1.48 (s, 3H), 1.46-1.41 (m, 1H), 1.19 (s,3H), 0.94-0.92 (m, 1H), 0.77-0.68 (m, 1H); LCMS m/z=509.06 (M+, 20%).

Intermediates in table-7 were synthesized by an analogous reactionprotocol as was used for the preparation of7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)-3-chloro-5-fluoroquinolin-2-amineusing the appropriate starting materials and at suitable temperature.

TABLE 7 Structure & IUPAC name- Intermediates used ¹H NMR & LCMS data

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3- chloro-6-fluoroquinolin- 2-amine ¹H NMR (400 MHz,DMSO-d₆) δ 8.16 (s, 1H), 8.07 (s, 1H), 7.50-7.40 (m, 2H), 7.14 (d, J =3.5 Hz, 1H), 7.09-7.01 (m, 3H), 6.67 (s, 1H), 6.62 (dd, J = 6.0, 3.6 Hz,1H), 5.20 (d, J = 7.2 Hz, 1H), 5.01 (s, 1H), 4.54 (d, J = 7.2 Hz, 1H),2.97-2.76 (m, 2H), 2.30- 2.20(m, 1H), 1.68-1.60 (m, 1H), 1.48 (s, 3H),1.24 (s, 3H), 1.20-1.14 (m, 1H), 0.97-0.94 (m, 1H), 0.76- 0.70 (m, 1H);LCMS m/z = 509.06 (M+, 30%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3- chloroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d₆)δ 8.15 (s, 1H), 8.08 (s, 1H), 7.58 (d, J = 8.2 Hz, 1H), 7.37 (d, J = 1.6Hz, 1H), 7.20-7.10 (m, 2H), 7.01 (s, 2H), 6.73-6.57 (m, 3H), 5.21 (dd, J= 7.1, 1.3 Hz, 1H), 5.01 (s, 1H), 4.52 (dd, J = 7.3, 1.5 Hz, 1H),2.86-2.81 (m, 2H), 2.32- 2.21 (m, 1H), 1.69-1.65 (m, 1H), 1.48 (s, 3H),1.47- 1.42 (m, 1H), 1.20 (s, 3H), 0.97-0.91 (m, 1H), 0.80-0.72 (m, 1H);LCMS m/z = 491.06 (M+, 100%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3- methoxyquinolin-2- amine ¹H NMR (400 MHz,DMSO-d₆) δ 8.08 (s, 1H), 7.50 (d, J = 8.1 Hz, 1H), 7.40-7.24 (m, 2H),7.18- 7.05 (m, 2H), 7.01 (s, 2H), 6.61 (d, J = 3.5 Hz, 1H), 6.29 (s,2H), 5.21 (dd, J = 7.2, 1.3 Hz, 1H), 5.02 (s, 1H), 4.52 (dd, J = 7.3,1.5 Hz, 1H), 3.89 (s, 3H), 2.88- 2.74 (m, 2H), 2.30-2.18 (m, 1H),1.72-1.60 (m, 1H), 1.48 (s, 3H), 1.46- 1.41 (m, 1H), 1.20 (s, 3H),0.98-0.91 (m, 1H), 0.79- 0.73 (m, 1H); LCMS m/z = 487.2 (M + 1, 50%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3- isopropylquinolin-2- amine ¹H NMR (400 MHz,DMSO-d₆) δ 8.08 (s, 1H), 7.83 (s, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.34(d, J = 1.5 Hz, 1H), 7.14 (dd, J = 7.6, 2.5 Hz, 2H), 7.02 (s, 2H), 6.69-6.59 (m, 3H), 5.27-5.16 (m, 1H), 5.01 (s, 1H), 4.53 (dd, J = 7.3, 1.5Hz, 1H), 3.10-3.0 (m, 1H), 2.91- 2.76 (m, 2H), 2.32-2.19 (m, 1H),1.72-1.60 (m, 1H), 1.48 (s, 3H), 1.45- 1.41 (m, 1H), 1.25-1.23 (m, 6H),1.20 (s, 3H), 0.96- 0.91 (m, 1H), 0.77-0.73 (m, 1H); LCMS m/z = 499.3(M + 1, 75%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3- chloro-8-fluoroquinolin- 2-amine LCMS m/z =509.12 (M+, 60%) 7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7- yl)-2,2-dimethyltetra-hydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)ethyl)-3-chloro-8-fluoroquinolin-2-amine

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3- methylquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6)δ 8.08 (s, 1H), 7.73 (s, 1H), 7.51 (d, J = 8.1 Hz, 1H), 7.34 (d, J = 1.6Hz, 1H), 7.13-7.07 (m, 2H), 7.01 (s, 2H), 6.61 (d, J = 3.5 Hz, 1H), 6.40(s, 2H), 5.21 (d, J = 7.2 Hz, 1H), 5.01 (s, 1H), 4.53 (dd, J = 7.2, 1.4Hz, 1H), 2.90-2.76 (m, 2H), 2.31-2.20 (m, 1H), 2.21 (s, 3H), 1.72-1.61(m, 1H), 1.48 (s, 3H), 1.47- 1.41 (m, 1H), 1.23 (s, 3H), 0.97-0.91 (m,1H), 0.80- 0.73 (m, 1H); LCMS m/z = 471.3 (M + 1, 90%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3- cyclopropylquinolin-2- amine ¹H NMR (400 MHz,DMSO-d6) δ 8.07 (s, 1H), 7.59 (s, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.32(d, J = 1.6 Hz, 1H), 7.17-7.05 (m, 2H), 7.02 (s, 1H), 6.61 (d, J = 3.5Hz, 1H), 6.46 (s, 2H), 5.21 (d, J = 7.2 Hz, 1H), 5.01 (s, 1H), 4.52 (dd,J = 7.3, 1.5 Hz, 1H), 2.90-2.73 (m, 2H), 2.30-2.18 (m, 1H), 1.86-1.74(m, 1H), 1.73- 1.60 (m, 1H), 1.51-1.41 (m, 4H), 1.26-1.22 (m, 4H),1.00-0.90 (m, 3H), 0.79- 0.71 (m, 1H), 0.68-0.60 (m, 2H); LCMS m/z =497.11 (M + 1, 15%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 2-Amino-7- bromoquinoline-3- carbonitrile ¹H NMR (400 MHz,DMSO-d6) δ 8.61 (s, 1H), 8.07 (s, 1H), 7.66 (d, J = 8.3 Hz, 1H), 7.38(s, 1H), 7.29- 7.19 (m, 1H), 7.12 (d, J = 3.5 Hz, 1H), 7.01 (s, 2H),6.89 (s, 2H), 6.61 (dd, J = 8.7, 3.5 Hz, 1H), 5.21 (d, J = 7.1 Hz, 1H),5.01 (s, 1H), 4.52 (dd, J = 7.0, 1.6 Hz, 1H), 2.89-2.83 (m, 2H),2.31-2.22 (m, 1H), 1.72- 1.60 (m, 1H), 1.48 (s, 3H), 1.45-1.40 (m, 1H),1.20 (s, 3H), 0.97-0.90 (m, 1H), 0.80-0.60 (m, 1H); LCMS m/z = 482.36(M + 1, 15%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3- fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6)δ 8.07 (s, 1H), 7.77 (d, J = 11.8 Hz, 1H), 7.57 (d, J = 8.2 Hz, 1H),7.37 (d, J = 1.6 Hz, 1H), 7.20-7.09 (m, 2H), 7.01 (s, 2H), 6.71 (s, 2H),6.60 (d, J = 3.5 Hz, 1H), 5.21 (dd, J = 7.2, 1.3 Hz, 1H), 5.02 (s, 1H),4.52 (dd, J = 7.4, 1.5 Hz, 1H), 2.87-2.77 (m, 2H), 2.31-2.20 (m, 1H),1.70-1.60 (m, 1H), 1.48 (s, 3H), 1.46-1.43 (m, 1H), 1.20 (s, 3H),0.96-0.92 (m, 1H), 0.82-0.69 (m, 1H); LCMS m/z = 475.3 (M + 1, 100%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-6- methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3-chloro- 5-fluoroquinolin-2- amine LCMSm/z = 522.94 (M+, 15%) 7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-amino-6-methyl-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyltetra-hydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)ethyl)-3-chloro-5-fluoroquinolin-2-amine

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-6- methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine & 7-Bromo-3-chloro-6- fluoroquinolin-2-amine LCMSm/z = 522.94 (M+, 10%) 7- (2-((3aR,3bR,4aS,5R,5aS)-5-(4-amino-6-methyl-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-tetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)- 3-chloro-6-fluoroquinolin-2-amine

7-((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl- 3b-vinyl- hexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7- Bromo-3-methyl- imidazo[1,2-a]pyridine LCMS m/z= 445.3 (M + 1, 70%) 7-((3aR,3bR,4aS,5R,5aS)-2,2-dimethyl-3b-(2-(3-methylimidazo[1,2- a]pyridin-7-yl)ethyphexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

7-((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl- 3b-vinyl- hexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 3-Bromo-6-fluoro- 7-iodoquinolin-2-amine LCMS m/z= 553.20 (M+, 100%) 7- (2-((3aR,3bR,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7- yl)-2,2-dimethyltetra-hydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)ethyl)-3-bromo-6-fluoroquinolin-2-amine

LCMS m/z = 755.59 (M + 2, 100%).

7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)-N-isopropylquinolin-2-amine

7-((3aR,3bS,4aS,5R,5aS)-2,2-Dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(150 mg, 0.480 mmol) in 9-BBN (0.5 molar, 3.84 ml, 1.921 mmol) washeated at 50° C. for 1 h under N₂ atmosphere. The reaction mixture wascooled to 25° C., then potassium phosphate tribasic (510 mg, 2.401 mmol)in water (0.5 ml) was added and stirred for 30 mins. A solution of7-bromo-N-isopropylquinolin-2-amine (0.127 g, 0.480 mmol) in THF (3 ml)was added, followed bydichloro[1,1′-bis(di-t-butylphosphino)ferrocene]palladium(II) (6.26 mg,9.60 μmol). The resulting mixture was stirred at 50° C. for 6 h. Thereaction mixture was diluted with water (10 ml) and extracted with ethylacetate (10 ml). Layers were separated, organic layer was washed withbrine (10 ml) and dried over anhydrous Na₂SO₄. The organic layer wasfiltered and concentrated in vacuo to give 1.5 g of crude compound. Thisresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution (0 to 10%) of 50% 7NNH₃/MeOH in dichloromethane to afford the title compound (0.12 g, 50.1%)as a pale yellow semisolid. LCMS m/z=499.2 (M+1, 40%).

Intermediates in table-8 were synthesized by an analogous reactionprotocol as was used for the preparation of7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)-N-isopropylquinolin-2-amineusing the appropriate starting materials and at suitable temperature.

TABLE 8 Structure & IUPAC name Intermediates used ¹H NMR & LCMS data

7-((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-N- cyclobutylquinolin-2- amine LCMS m/z= 511.3 (M + 1, 40%) 7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyltetra-hydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)ethyl)-N-cyclobutylquinolin-2-amine

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-3-(1,1- difluoroethyl)quinolin- 2-amine¹H NMR (400 MHz, DMSO-d₆) δ 8.15 (s, 1H), 8.08 (d, J = 1.4 Hz, 1H), 7.69(d, J = 8.2 Hz, 1H), 7.38 (s, 1H), 7.22- 7.11 (m, 2H), 7.01 (s, 2H),6.61 (dd, J = 3.6, 1.4 Hz, 1H), 6.23 (s, 2H), 5.22 (d, J = 7.1 Hz, 1H),5.02 (s, 1H), 4.53 (d, J = 7.1 Hz, 1H), 2.92-2.78 (m, 2H), 2.32-2.22 (m,1H), 2.08 (t, J = 19.1 Hz, 3H), 1.74-1.60 (m, 1H), 1.48 (s, 3H),1.46-1.41 (m, 1H), 1.24 (s, 3H), 0.97-0.92 (m, 1H), 0.79- 0.71 (m, 1H);LCMS m/z = 520.94 (M+, 50%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 7-Bromo-N- (cyclopropylmethyl) quinolin-2-amine¹H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.78 (d, J = 8.9 Hz, 1H), 7.51(d, J = 8.1 Hz, 1H), 7.39 (d, J = 1.6 Hz, 1H), 7.19-7.05 (m, 3H), 7.02(s, 2H), 6.73 (d, J = 8.9 Hz, 1H), 6.61 (d, J = 3.6 Hz, 1H), 5.21 (dd, J= 7.2, 1.3 Hz, 1H), 5.02 (s, 1H), 4.52 (dd, J = 7.3, 1.5 Hz, 1H), 3.26(t, J = 6.1 Hz, 2H), 2.90-2.74 (m, 2H), 2.34-2.22 (m, 1H), 1.75-1.59 (m,2H), 1.49 (s, 3H), 1.48-1.44 (m, 1H), 1.20 (s, 3H), 0.94 (t, J = 4.6 Hz,1H), 0.77- 0.70 (m, 1H), 0.51-0.43 (m, 2H), 0.29-0.22 (m, 2H); LCMS m/z= 511.12 (M + 1, 100%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine and 6-Bromo-3,3- dimethyl-2- (methylthio)-3H-indole¹H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.34-7.26 (m, 2H), 7.12 (d, J= 3.5 Hz, 1H), 7.08-6.94 (m, 3H), 6.61 (d, J = 3.5 Hz, 1H), 5.22- 5.15(m, 1H), 5.02 (s, 1H), 4.52 (dd, J = 7.2, 1.5 Hz, 1H), 2.81-2.69 (m,2H), 2.59 (s, 3H), 2.29-2.16 (m, 1H), 1.68- 1.56 (m, 1H), 1.48 (s, 3H),1.45-1.41 (m, 1H), 1.27 (s, 6H), 1.20 (s, 3H), 0.94 (t, J = 4.7 Hz, 1H),0.80-0.71 (m, 1H); LCMS m/z = 504.31 (M + 1, 100%)

7-((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclopropa[3,4]cyclopenta [1,2-d][1,3]dioxol-5- yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine and 6′-Bromospiro [cyclobutane-1,3′-indol]-2′-amine. LCMS m/z = 485.3 (M + 1, 70%)6′-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyltetra-hydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)ethyl)spiro[cyclobutane-1,3′-indol]-2′- amine

3-Bromo-7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)-N-(4-methoxybenzyl)quinolin-2-amine

4-Chloro-7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (2.9 g, 8.74mmol) in 9-BBN (0.5 molar, 87 ml, 43.7 mmol) was stirred at 70° C. for 1h. The reaction mixture was cooled to 25° C., then potassium phosphatetribasic (5.57 g, 26.2 mmol) in water (45 ml) was added and stirred for30 mins. A solution of3-bromo-7-iodo-N-(4-methoxybenzyl)quinolin-2-amine (4.72 g, 10.05 mmol)in THF (60 ml) was added, followed by PdCl₂(dppf)-CH₂Cl₂ (0.357 g, 0.437mmol). The resulting mixture was stirred at 70° C. for 3 h. The reactionmixture was diluted with water (50 ml) and extracted with ethyl acetate(50 ml). Layers were separated, organic layer was washed with brine (50ml) and dried over anhydrous Na₂SO₄. The organic layer was filtered andconcentrated in vacuo to give 3.5 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0 to 30%) of ethyl acetatein petroleum ether to afford the title compound (3.1 g, 52.5%) as anoff-white solid. ¹H NMR (400 MHz, DMSO-d₆) δ 8.68 (s, 1H), 8.33 (s, 1H),7.73 (d, J=3.7 Hz, 1H), 7.56 (d, J=8.2 Hz, 1H), 7.43 (d, J=1.6 Hz, 1H),7.37-7.31 (m, 2H), 7.25-7.12 (m, 1H), 7.15 (dd, J=8.2, 1.6 Hz, 1H),6.90-6.83 (m, 2H), 6.70 (d, J=3.7 Hz, 1H), 5.27 (dd, J=7.2, 1.3 Hz, 1H),5.12 (s, 1H), 4.71-4.56 (m, 3H), 3.70 (s, 3H), 2.90-2.75 (m, 2H),2.38-2.26 (m, 1H), 1.63-1.58 (m, 1H), 1.55-1.51 (m, 1H), 1.49 (s, 3H),1.20 (s, 3H), 0.95 (t, J=4.7 Hz, 1H), 0.79-0.72 (m, 1H); LCMS m/z=674.1(M−1, 100%).

Intermediates in table-9 were synthesized by an analogous reactionprotocol as was used for the preparation of3-bromo-7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)-N-(4-methoxybenzyl)quinolin-2-amineusing the appropriate starting materials.

TABLE 9 ¹H NMR & LCMS Structure & IUPAC name Intermediates used data

4-chloro-7- ((3aR,3bR,4aS,5R,5aS)- 2,2-dimethyl-3b-(prop-1-en-2-yl)hexahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidine and 7-Bromo-3-chloro-5-fluoro-N-(4- methoxybenzyl)quinolin- 2-amine LCMS m/z = 662.10 (M+,100%) 3-Chloro-7-(2-((3aR,3bS,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)- 2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)propyl)-5-fluoro-N-(4-methoxybenzyl)quinolin-2- amine

4-Chloro-7- ((3aR,3bR,4aS,5R,5aS)- 3b-(1-cyclopropylvinyl)- 2,2-dimethylhexahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidine and 7-Bromo-3-chloro-5-fluoro-N-(4- methoxybenzyl)quinolin- 2-amine ¹H NMR (400 MHz, DMSO-d₆) δ8.62 (s, 1H), 8.16 (d, J = 3.6 Hz, 1H), 7.78-7.71 (m, 1H), 7.61 (dd, J =10.1, 5.1 Hz, 1H), 7.40-7.30 (m, 3H), 7.09-7.03 (m, 1H), 6.86 (dd, J =8.6, 3.2 Hz, 2H), 6.78- 6.74(m, 1H), 5.53 (t, J = 7.2 Hz, 2H), 5.34 (d,J = 7.0 Hz, 1H), 5.16 (s, 1H), 4.63 (d, J = 6.5 Hz, 1H), 3.70 (s, 3H),2.98-2.88 (m, 2H), 1.73-1.68 (m, 1H), 1.53 (d, J = 7.4 Hz, 4H), 1.26-1.22 (m, 4H), 0.91- 0.86 (m, 1H), 0.63- 0.55 (m, 1H), 0.43- 0.33 (m,2H), 0.22- 0.12 (m, 2H).

4-chloro-7- ((3aR,3bR,4aS,5R,5aS)- 2,2-dimethyl-3b-(prop-1-en-2-yl)hexahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidine & 3-Bromo-7-iodo-N-(4-methoxybenzyl)quinolin- 2-amine LCMS m/z = 687.98 (M − 1, 80%); 689.98(M + 1, 100%) 3-Bromo-7-(2-((3aR3bS,4aS,5R5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)- 2,2-dimethyltetra-hydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)propyl)-N-(4- methoxybenzyl)quinolin-2-amine

7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)-8-fluoroquinolin-2-amine

4-chloro-7-((3aR,3bS,4aS,5R,5aS)-2,2-dimethyl-3b-vinylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine (0.38 g, 1.145mmol) in 9-BBN (0.5 molar, 9.16 ml, 4.58 mmol) was stirred at 70° C. for8 h. The reaction mixture was cooled to 25° C., then potassium phosphatetribasic (0.729 g, 3.44 mmol) in water (6 ml) was added and stirred for30 mins. A solution of 7-bromo-8-fluoroquinolin-2-amine (0.304 g, 1.26mmol) in THF (30 ml) was added, followed by[1,1′-bis(di-tert-butylphosphino) ferrocene] dichloropalladium(II)(0.022 g, 0.034 mmol). The resulting mixture was stirred at 70° C. for 7h. The reaction mixture was diluted with water (20 ml) and extractedwith ethyl acetate (20 ml). Layers were separated, organic layer waswashed with brine (20 ml) and dried over anhydrous Na₂SO₄. The organiclayer was filtered and concentrated in vacuo to give 0.5 g of crudecompound. This residue was purified by combiflash (R_(f)200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0 to 50%) of ethyl acetate in petroleum ether to afford thetitle compound (0.12 g, 21.21%) as an off-white solid. ¹H NMR (400 MHz,DMSO-d6) δ 8.67 (s, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.75 (d, J=3.6 Hz, 1H),7.36 (d, J=8.1 Hz, 1H), 7.14-7.05 (m, 1H), 6.79-6.70 (m, 2H), 6.64 (s,2H), 5.27 (d, J=7.2 Hz, 1H), 5.13 (s, 1H), 4.69 (d, J=7.2 Hz, 1H),2.96-2.77 (m, 2H), 2.31-2.22 (m, 1H), 1.70-1.60 (m, 1H), 1.59-1.54 (m,1H), 1.50 (s, 3H), 1.21 (s, 3H), 0.99 (t, J=4.7 Hz, 1H), 0.83-0.77 (m,1H); LCMS m/z=494 (M+, 100%)

Intermediates in table-10 were synthesized by an analogous reactionprotocol as was used for the preparation of7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)-8-fluoroquinolin-2-amineusing the appropriate starting materials and at suitable temperature.

TABLE 10 Structure & IUPAC name Intermediates used ¹H NMR & LCMS data

4-Chloro-7- ((3aR,3bS,4aS,5R,5aS)- 2,2-dimethyl-3b- vinylhexahydro-cyclopropa[3,4]cyclo- penta[1,2- d][1,3]dioxol-5-yl)- 7H-pyrrolo[2,3-d]pyrimidine & 7- Bromo-N-(4- methoxybenzyl) quinolin-2-amine ¹H NMR(400 MHz, Chloroform-d) δ 8.68 (s, 1H), 7.82 (d, J = 8.9 Hz, 1H), 7.60(d, J = 1.5 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.41-7.33 (m, 2H),7.21-7.14 (m, 2H), 6.97- 6.84 (m, 2H), 6.65-6.57 (m, 2H), 5.23 (dd, J =7.3, 1.4 Hz, 1H), 5.15 (s, 1H), 4.70-4.62 (m, 3H), 3.83 (s, 3H), 3.11-2.86 (m, 2H), 2.48-2.37 (m, 1H), 1.83-1.76 (m, 1H), 1.55 (s, 3H), 1.50(dd, J = 4.8, 1.5 Hz, 1H), 1.28 (s, 3H), 1.16 (t, J = 5.0 Hz, 1H),0.86-0.78 (m, 1H); LCMS m/z = 596.20 (M+, 100%)

4-Chloro-7- ((3aR,3bS,4aS,5R,5aS)- 2,2-dimethyl-3b- vinylhexahydro-cyclopropa[3,4]cyclo- penta[1,2- d][1,3]dioxol-5-yl)- 7H-pyrrolo[2,3-d]pyrimidine and 7- Bromo-N- methylquinolin-2- amine ¹H NMR (400 MHz,DMSO-d₆) δ 8.69 (s, 1H), 7.77 (d, J = 8.9 Hz, 1H), 7.74 (d, J = 3.7 Hz,1H), 7.51 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 1.6 Hz, 1H), 7.07 (dd, J =8.1, 1.7 Hz, 1H), 6.93 (d, J = 5.9 Hz, 1H), 6.71 (d, J = 3.6 Hz, 1H),6.67 (d, J = 8.9 Hz, 1H), 5.27 (dd, J = 7.2, 1.3 Hz, 1H), 5.13 (s, 1H),4.67 (dd, J = 7.3, 1.5 Hz, 1H), 2.88 (d, J = 4.7 Hz, 3H), 2.85-2.74 (m,2H), 2.36-2.30 (m, 1H), 1.71-1.65 (m, 1H), 1.57-1.52 (m, 1H), 1.50 (s,3H), 1.21 (s, 3H), 0.96 (t, J = 4.7 Hz, 1H), 0.82-0.76 (m, 1H); LCMS m/z= 490.24 (M+, 60%)

4-Chloro-7- ((3aR,3bS,4aS,5R,5aS)- 2,2-dimethyl-3b- vinylhexahydro-cyclopropa[3,4]cyclo- penta[1,2- d][1,3]dioxol-5-yl)- 7H-pyrrolo[2,3-d]pyrimidine & 7- Bromo-N-(4- methoxybenzyl) quinazolin-2-amine ¹H NMR(400 MHz, DMSO-d₆) δ 9.04 (s, 1H), 8.68 (s, 1H), 7.79 (s, 1H), 7.74 (d,J = 3.7 Hz, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.35 (s, 1H), 7.30 (d, J =8.2 Hz, 2H), 7.17 (dd, J = 8.3, 1.6 Hz, 1H), 6.89-6.83 (m, 2H), 6.71 (d,J = 3.7 Hz, 1H), 5.27 (d, J = 7.1 Hz, 1H), 5.13 (s, 1H), 4.71-4.64 (m,1H), 4.52 (d, J = 6.3 Hz, 2H), 3.71 (s, 3H), 2.90-2.80 (m, 2H),2.37-2.27 (m, 1H), 1.67-1.62 (m, 1H), 1.56-1.52 (m, 1H), 1.49 (s, 3H),1.20 (s, 3H), 0.95 (t, J = 4.6 Hz, 1H), 0.79-0.74 (m, 1H); LCMS m/z =597.3 (M+, 100%)

7- ((3aR,3bS,4aS,5R,5aS)- 2,2-Dimethyl-3b- vinylhexahydrocyclo- propa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-4- methyl-7H- pyrrolo[2,3-d]pyrimidine and 7- Bromo-3-chloro-5- fluoroquinolin-2- amine LCMS m/z =508.19 (M+, 80%)

7-(1-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethoxy)-N-methylquinolin-2-amine

To a stirred solution of1-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethan-1-ol(0.2 g, 0.596 mmol), 2-(methylamino)quinolin-7-ol (0.145 g, 0.834 mmol)and triphenylphosphine (0.469 g, 1.787 mmol) at 0° C. was added DEAD(0.283 ml, 1.787 mmol) slowly and stirred for 30 min. The resultingmixture was stirred at 25° C. for 1 h. The solvent was evaporated underreduced pressure and the residue was purified by combiflash (R_(f)200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0 to 20%) of ethyl acetate in petroleum ether to afford thetitle compound (0.1 g, 34.1%) as an off-white solid. LCMS m/z=492.2 (M+,100%).

7-(((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methoxy)-N-methylquinolin-2-amine

To a stirred solution of((3aR,6R,6aS)-6-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol(0.25 g, 0.777 mmol), 2-(methylamino)quinolin-7-ol (0.338 g, 1.942 mmol)and triphenylphosphine (0.611 g, 2.331 mmol) in THF (20 ml) was addedDEAD (0.369 ml, 2.331 mmol) dropwise at 0° C. The resulting mixture wasstirred at 25° C. for 20 h. The solvent was evaporated under reducedpressure and the residue was purified by combiflash (R_(f)200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0 to 70%) of ethyl acetate in petroleum ether (0.2 g, 53.9%) asan off-white solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.66 (s, 1H), 7.74 (d,J=8.8 Hz, 1H), 7.53 (d, J=1.7 Hz, 1H), 7.51 (d, J=3.5 Hz, 1H), 7.07 (d,J=2.5 Hz, 1H), 6.95 (d, J=5.0 Hz, 1H), 6.85 (dd, J=8.7, 2.5 Hz, 1H),6.69-6.51 (m, 2H), 5.87 (s, 1H), 5.78 (s, 1H), 5.55-5.42 (m, 1H),5.04-4.85 (m, 2H), 4.74-4.63 (m, 1H), 2.89 (d, J=4.7 Hz, 3H), 1.49 (s,3H), 1.24 (s, 3H); LCMS m/z=479.3 (M+1, 100%).

3-Bromo-7-(((3aR,3bR,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)methoxy)-N-(4-methoxybenzyl)quinolin-2-amine

To a stirred solution of((3aR,3bR,4aS,5R,5aS)-5-(4-chloro-7-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)methanol(0.09 g, 0.268 mmol), 3-bromo-2-((4-methoxybenzyl)amino)quinolin-7-ol(0.106 g, 0.295 mmol) and triphenylphosphine (0.176 g, 0.670 mmol) inTHF (8 ml), was added DEAD (0.106 ml, 0.670 mmol) dropwise at 0° C. andstirred for 30 min. The resulting mixture stirred for at 25° C. for 14h. The solvent was evaporated under reduced pressure and the residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® Rf column with gradient elution (0 to 60%) of ethyl acetate inpetroleum ether (0.12 g, 66.1%) as an off-white solid. LCMS m/z=677.97(M+1, 100%).

3-Bromo-7-((E)-1-((3aR,3bS,4aS,5R,5aS)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)prop-1-en-2-yl)-N-(4-methoxybenzyl)quinolin-2-amine

A mixture of4-chloro-7-((3aR,3bR,4aS,5R,5aS)-3b-((E)-2-iodoprop-1-en-1-yl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine(0.12 g, 0.254 mmol), triphenylphosphine (6.67 mg, 0.025 mmol),3-bromo-N-(4-methoxybenzyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine(0.179 g, 0.382 mmol), sodium carbonate (0.054 g, 0.509 mmol) andPd(OAc)₂ (2.86 mg, 0.013 mmol) in DMF (4 ml) and water (1 ml) wasstirred at 25° C. for 16 h. The reaction mixture was diluted with water(20 ml) and extracted with ethyl acetate (20 ml). Layers were separated,organic layer was washed with brine (20 ml) and dried over anhydrousNa₂SO₄. The organic layer was filtered and concentrated in vacuo to give0.3 g of crude compound. This residue was purified by combiflash(R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f) column withgradient elution (0 to 15%) of ethyl acetate in petroleum ether toafford the title compound (0.13 g, 74.4%) as an off-white solid. LCMSm/z=687.98 (M+1, 100%).

N7-(((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methyl)-N2-(4-methoxybenzyl)quinoline-2,7-diamine

To a stirred solution of(3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxole-6-carbaldehyde(0.18 g, 0.563 mmol) and N2-(4-methoxybenzyl)quinoline-2,7-diamine(0.157 g, 0.563 mmol) in methanol (5 ml) was added acetic acid (0.1 mL)at 25° C. and stirred for 2 h. Sodium cyanoborohydride (0.106 g, 1.689mmol) was added stirred for 16 h. The reaction was quenched by additionof sat. NH₄Cl (15 mL). The reaction mixture was concentrated underreduced pressure and the residue was diluted with ethyl acetate (40 mL).The organic phase was washed with water (30 ml), saturated aqueoussodium bicarbonate (30 ml) and brine (30 ml) successively. Dried theorganic layer over anhydrous Na₂SO₄, filtered and concentrated underreduced pressure to give 0.2 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0 to 15%) of methanol indichloromethane to afford the title compound (0.15 g, 45.7%) as a paleyellow solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.66 (s, 1H), 7.59 (d, J=8.8Hz, 1H), 7.48 (d, J=3.7 Hz, 1H), 7.30 (m, 3H), 7.10 (t, J=5.8 Hz, 1H),6.92-6.86 (m, 2H), 6.65 (dd, J=8.6, 2.3 Hz, 1H), 6.57 (d, J=2.2 Hz, 1H),6.51 (d, J=3.7 Hz, 1H), 6.45 (d, J=8.7 Hz, 1H), 5.72 (s, 1H), 5.69 (s,1H), 5.38 (d, J=5.7 Hz, 1H), 4.65-4.52 (m, 1H), 4.55 (d, J=5.8 Hz, 2H),4.13-3.93 (m, 3H), 3.72 (s, 3H), 1.48 (s, 3H), 1.30 (s, 3H); LCMSm/z=583.4 (M+, 100%).

N7-(((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methyl)-N2-(4-methoxybenzyl)-N7-methylquinoline-2,7-diamine

To a stirred solution ofN2-(4-methoxybenzyl)-N7-methylquinoline-2,7-diamine in DMF (2 ml) wasadded K₂CO₃ (0.058 g, 0.420 mmol) at 0° C. slowly followed by((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methyl 4-methylbenzenesulfonate (0.1 g, 0.210 mmol) andstirred the reaction mixture for 10 mins. The resulting mixture wasstirred at 25° C. for 16 h. The reaction mixture was diluted with water(20 ml) and extracted with ethyl acetate (20 ml). Layers were separated,organic layer was washed with brine (20 ml) and dried over anhydrousNa₂SO₄. The organic layer was filtered and concentrated in vacuo to give0.3 g of crude compound. This residue was purified by combiflash(R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f) column withgradient elution (0 to 7%) of ethyl acetate in petroleum ether to affordthe title compound (0.025 g, 19.93%) as a colourless oil. LCMSm/z=597.29 (M+, 80%).

7-((((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methy)thio)-N-(4-methoxybenzyl)quinolin-2-amine

To a stirred solution of 2-((4-methoxybenzyl)amino)quinoline-7-thiol(125 mg, 0.422 mmol) in DMSO (3 ml) at 0° C. was added Cs₂CO₃ (302 mg,0.928 mmol) and((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methyl 4-methylbenzenesulfonate (201 mg, 0.422 mmol). Theresulting mixture was stirred at 25° C. for 3 h. The reaction mixturewas diluted with water (20 ml) and extracted with ethyl acetate (20 ml).Layers were separated, organic layer was washed with brine (20 ml) anddried over anhydrous Na₂SO₄. The organic layer was filtered andconcentrated in vacuo to give 0.3 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0 to 20%) of ethyl acetatein petroleum ether to afford the title compound (0.112 g, 44.3%) as anoff-white solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.60 (s, 1H), 7.85 (d,J=8.9 Hz, 1H), 7.60-7.48 (m, 3H), 7.33-7.26 (m, 2H), 7.19 (dd, J=8.3,1.9 Hz, 1H), 6.85-6.79 (m, 3H), 6.48 (d, J=3.7 Hz, 1H), 6.06 (d, J=3.6Hz, 1H), 5.72 (s, 1H), 5.65 (s, 1H), 5.43 (d, J=5.7 Hz, 1H), 4.54 (d,J=5.7 Hz, 2H), 4.48 (d, J=5.7 Hz, 1H), 4.22 (d, J=15.3 Hz, 1H),3.77-3.70 (m, 1H), 3.68 (s, 3H), 1.43 (s, 3H), 1.28 (s, 3H); LCMSm/z=600.21 (M+, 100%).

3-Chloro-7-(1-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethoxy)-5-fluoro-N-(4-methoxybenzyl)quinolin-2-amine

To a stirred solution of1-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethan-1-ol(0.7 g, 2.085 mmol),3-chloro-5-fluoro-2-((4-methoxybenzyl)amino)quinolin-7-ol (0.416 g,1.251 mmol) and triphenylphosphine (1.640 g, 6.25 mmol) in THF (10 ml),was added DEAD (0.990 ml, 6.25 mmol) dropwise at 0° C. and stirred for30 mins. The resulting mixture stirred at 25° C. for 16 h. The solventwas evaporated under reduced pressure and this residue was purified bycombiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0 to 15%) of ethyl acetate in petroleumether to afford the title compound (0.5 g, 36.9% yield) as an off-whitesolid. LCMS m/z=650.3 (M+, 100%).

3-chloro-7-(((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methoxy)-5-fluoro-N-(4-methoxybenzyl)quinolin-2-amine

Cesium carbonate (558 mg, 1.713 mmol) was added to a solution of((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methyl4-methylbenzenesulfonate (272 mg, 0.571 mmol) and3-chloro-5-fluoro-2-((4-methoxybenzyl)amino) quinolin-7-ol (190 mg,0.571 mmol) in DMF (4 ml) at 0° C. and stirred at 25° C. for 1 h. Icecold water (20 ml) was added to the reaction mixture and stirred for 10minutes, precipitated solid was filtered, washed with water and driedunder vacuum to afford the title compound (300 mg, 83%) as a brownsolid. ¹H NMR (400 MHz, DMSO-d6) δ 8.64 (s, 1H), 8.11 (s, 1H), 7.65 (t,J=6.1 Hz, 1H), 7.50 (d, J=3.7 Hz, 1H), 7.36-7.30 (m, 2H), 6.94 (d, J=2.3Hz, 1H), 6.89-6.79 (m, 3H), 6.60 (d, J=3.7 Hz, 11H), 5.87 (s, 11H), 5.78(s, 1H), 5.48 (d, J=5.7 Hz, 1H), 5.05-4.89 (m, 2H), 4.70 (d, J=5.7 Hz,1H), 4.64 (d, =6.1 Hz, 2H), 3.71 (s, 3H), 1.45 (s, 3H), 1.30 (s, 3H);LCMS m/z=636.34 (M+, 100%).

Intermediates in table-11 were synthesized by ananalogous reactionprotocol as was used for the preparation of3-chloro-7-(((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methoxy)-5-fluoro-N-(4-methoxybenzyl)quinolin-2-amineusing the appropriate starting materials and at suitable temperature.

TABLE 11 Structure & IUPAC name Intermediates used ¹H NMR & LCMS data

((3aS,4R,6aR)-4-(4-((4- methoxybenzyl)amino)- 7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,5- trimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)methyl 4- methylbenzenesulfonate &3-chloro-5-fluoro-2- ((4- methoxybenzyl)amino) quinolin-7-ol LCMS m/z =751.61 (M+, 100%).

((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol- 6-yl)methyl 4-methylbenzenesulfonate & 2-(bis(4- methoxybenzyl)amino)-3-chloroquinoline-7- thiol ¹H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 1H),8.41 (s, 1H), 7.74 (d, J = 8.6 Hz, 1H), 7.67 (d, J = 1.8 Hz, 1H), 7.43(dd, J = 8.5, 1.9 Hz, 1H), 7.26-7.20 (m, 4H), 6.81-6.75 (m, 4H), 6.38(d, J = 3.7 Hz, 1H), 5.98 (d, J = 3.6 Hz, 1H), 5.72 (s, 1H), 5.63 (s,1H), 5.44 (d, J = 5.7 Hz, 1H), 4.57-4.42 (m, 5H), 4.28 (d, J = 15.4 Hz,1H), 3.82-3.76 (m, 1H), 3.64 (s, 6H), 1.42 (s, 3H), 1.28 (s, 3H); LCMSm/z = 754.49 (M+, 100%)

((3aR,3bR,4aS,5R,5aS)- 5-(4-chloro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol- 3b(3aH)-yl)methyl 4- methylbenzenesulfonate & 2-((4-methoxybenzyl)amino) quinoline-7-thiol ¹H NMR (400 MHz, Chloroform-d) δ8.68 (s, 1H), 7.76 (d, J = 8.9 Hz, 1H), 7.64 (d, J = 1.8 Hz, 1H), 7.48(d, J = 8.3 Hz, 1H), 7.39 (d, J = 3.6 Hz, 1H), 7.37-7.32 (m, 2H), 7.20(dd, J = 8.4, 1.9 Hz, 1H), 6.93-6.87 (m, 2H), 6.59 (d, J = 8.8 Hz, 1H),6.55 (d, J = 3.6 Hz, 1H), 5.39 (dd, J = 7.2, 1.5 Hz, 1H), 5.21 (s, 1H),4.65 (d, J = 5.3 Hz, 2H), 4.64-4.60 (m, 1H), 3.82 (s, 3H), 3.62 (d, J =13.3 Hz, 1H), 3.43 (d, J = 13.3 Hz, 1H), 1.76-1.73 (m, 1H), 1.60 (s,3H), 1.33- 1.30 (m, 1H), 1.26 (s, 3H), 1.12-1.06 (m, 1H); LCMS m/z =614.21 (M+, 100%)

3-Chloro-7-(((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,6a-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methoxy)-5-fluoro-N-(4-methoxybenzyl)quinolin-2-amine

To a stirred solution of((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,6a-trimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)methanol (250 mg, 0.745 mmol) and3-chloro-5-fluoro-2-((4-methoxybenzyl)amino)quinolin-7-ol (297 mg, 0.893mmol) in toluene (2 ml) was added triphenyl phosphine (234 mg, 0.893mmol) and stirred for 5 minutes then added DEAD (0.118 ml, 0.745 mmol)dropwise at 25° C. and reaction mixture was stirred at 90° C. for 2hours. The volatiles were removed in vacuo and obtained residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0 to 50%) of ethyl acetatein petroleum ether to afford the title compound (420 mg, 87%) as aoff-white solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.12 (s, 1H),7.69 (t, J=6.1 Hz, 1H), 7.48 (d, J=3.7 Hz, 1H), 7.42-7.36 (m, 1H),7.36-7.30 (m, 2H), 6.97 (d, J=2.2 Hz, 1H), 6.88-6.86 (m, 2H), 6.62 (d,J=3.6 Hz, 1H), 5.86 (d, J=2.8 Hz, 1H), 5.68 (d, J=2.5 Hz, 1H), 5.08 (d,J=15.5 Hz, 1H), 4.89 (d, J=15.5 Hz, 1H), 4.65 (d, J=6.0 Hz, 2H), 4.25(s, 1H), 3.70 (s, 3H), 1.55 (s, 3H), 1.41 (s, 3H), 1.34 (s, 3H); LCMSm/z=650.34 (M+, 100%).

7-(2-((3aS,4R,6aR)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethyl)-N-methylquinolin-2-amine

A mixture of7-(2-((3aS,4R,6aR)-4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethyl)-N-methylquinolin-2-amine(0.100 g, 0.210 mmol) in dioxane (3 ml) was added aq. ammonia (0.227 ml,10.50 mmol) at 25° C. and stirred the reaction mixture at 130° C. for 16h. The reaction mixture was diluted with brine (20 ml) and extractedwith ethyl acetate (20 ml). Layers were separated, the organic layer wasdried over anhydrous Na₂SO₄., filtered and concentrated in vacuo to give0.15 g of crude compound. The obtained residue was purified bycombiflash (R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f)column with gradient elution (0 to 5%) of methanol in dicholomethane toafford the title compound (0.07 g, 73%) as an off-white solid. LCMSm/z=457.2 (M+1; 40%).

Intermediates in table-12 were synthesized by an analogous reactionprotocol as was used for the preparation of7-(2-((3aS,4R,6aR)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethyl)-N-methylquinolin-2-amineusing the appropriate starting materials (Instead of aq.NH₃, 7N NH₃ inMeOH could also be used).

TABLE 12 Structure & IUPAC name Intermediate used ¹H NMR & LCMS data

7-(2-((3aS,4R,6aR)-4-(4- Chloro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-N-cyclobutylquinolin-2- amine ¹H NMR (400 MHz, Chloroform- d) δ 8.35 (s,1H), 7.86 (d, J = 8.9 Hz, 1H), 7.58-7.53 (m, 2H), 7.15 (dd, J = 8.2, 1.7Hz, 1H), 6.62 (d, J = 8.9 Hz, 1H), 6.31 (d, J = 3.6 Hz, 1H), 6.09 (d, J= 3.6 Hz, 1H), 5.75 (s, 1H), 5.51-5.45 (m, 2H), 5.26 (d, J = 6.0 Hz,1H), 5.15 (s, 2H), 4.47 (d, J = 5.7 Hz, 1H), 4.45- 4.37 (m, 1H),3.19-3.01 (m, 2H), 2.87-2.68 (m, 2H), 2.57- 2.46 (m, 2H), 2.02-1.93 (m,2H), 1.89-1.79 (m, 2H), 1.50 (s, 3H), 1.37 (s, 3H); LCMS m/z = 497.3(M + 1; 70%).

7-(2-((3aS,4R,6aR)-4-(4- Chloro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-3-fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.05 (s, 1H), 7.79(d, J = 11.8 Hz, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.41 (s, 1H), 7.19 (d, J= 8.2 Hz, 1H), 6.96 (s, 2H), 6.72 (s, 2H), 6.35- 6.31 (m, 2H), 5.54 (s,1H), 5.50 (s, 1H), 5.29 (d, J = 5.9 Hz, 1H), 4.35 (d, J = 5.7 Hz, 1H),3.10-2.93 (m, 2H), 2.70-2.60 (m, 2H), 1.37 (s, 3H), 1.24 (s, 3H); LCMSm/z = 461.3 (M + 1; 60%).

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)quinolin-2- amine ¹H NMR (400 MHz,DMSO-d6) δ 8.17 (s, 1H), 8.05 (s, 1H), 7.61 (d, J = 8.3 Hz, 1H), 7.41(d, J = 1.6 Hz, 1H), 7.19 (dd, J = 8.2, 1.7 Hz, 1H), 6.98 (s, 2H), 6.69(s, 2H), 6.41 (d, J = 3.6 Hz, 1H), 6.35 (d, J = 3.5 Hz, 1H), 5.55 (s,1H), 5.51 (s, 1H), 5.29 (d, J = 5.7 Hz, 1H), 4.36 (d, J = 5.7 Hz, 1H),3.09- 2.94 (m, 2H), 2.72-2.56 (m, 2H), 1.37 (s, 3H), 1.28 (s, 3H); LCMSm/z = 477.05 (M+; 20%).

3-Bromo-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-N-(4- methoxybenzyl)quinolin-2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.07 (s, 1H), 7.60 (d,J = 8.2 Hz, 1H), 7.45 (s, 1H), 7.38- 7.31 (m, 2H), 7.22-7.16 (m, 2H),7.01 (s, 2H), 6.88-6.82 (m, 2H), 6.52 (d, J = 3.5 Hz, 1H), 6.40 (d, J =3.6 Hz, 1H), 5.56 (s, 1H), 5.52 (s, 1H), 5.30 (d, J = 5.7 Hz, 1H),4.66-4.61 (m, 2H), 4.38 (d, J = 5.6 Hz, 1H), 3.69 (s, 3H), 3.06- 2.93(m, 2H), 2.70-2.59 (m, 2H), 1.38 (s, 3H), 1.27 (s, 3H); LCMS m/z =641.97 (M+; 60%).

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR(400 MHz, DMSO-d6) δ 8.17 (d, J = 0.7 Hz, 1H), 8.05 (s, 1H), 7.26 (s,1H), 7.05 (dd, J = 11.1, 1.4 Hz, 1H), 7.01-6.91 (m, 4H), 6.41 (d, J =3.5 Hz, 1H), 6.35 (d, J = 3.5 Hz, 1H), 5.54 (s, 1H), 5.51 (s, 1H), 5.30(d, J = 5.7 Hz, 1H), 4.37 (d, J = 5.7 Hz, 1H), 3.07- 2.95 (m, 2H),2.71-2.56 (m, 2H), 1.37 (s, 3H), 1.27 (s, 3H); LCMS m/z = 495.05 (M+;40%). 7-(2-((3aS,4R,6aR)-4-(4-Amino- 7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-chloro-5-fluoroquinolin- 2-amine

¹H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.05 (s, 1H), 7.25 (s, 1H),7.04 (dd, J = 11.0, 1.4 Hz, 1H), 6.97 (s, 2H), 6.86 (s, 2H), 6.43 (d, J= 3.5 Hz, 1H), 6.37 (d, J = 3.5 Hz, 1H), 5.55 (s, 1H), 5.51 (s, 1H),5.30 (d, J = 5.7 Hz, 1H), 4.38 (d, J = 5.7 Hz, 1H), 3.08- 2.95 (m, 2H),2.71-2.58 (m, 2H), 1.37 (s, 3H), 1.28 (s, 3H); LCMS m/z = 541.20 (M + 2;100%) 7-(2-((3aS,4R,6aR)-4-(4-Amino- 7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-bromo-5-fluoroquinolin- 2-amine

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-6- fluoroquinolin-2-amine ¹H NMR(400 MHz, DMSO-d6) δ 8.17 (s, 1H), 8.06 (s, 1H), 7.53- 7.44 (m, 2H),6.99 (s, 2H), 6.71 (s, 2H), 6.52 (d, J = 3.5 Hz, 1H), 6.40 (d, J = 3.5Hz, 1H), 5.57 (s, 1H), 5.55 (s, 1H), 5.32 (d, J = 5.7 Hz, 1H), 4.40 (d,J = 5.7 Hz, 1H), 3.12- 2.99 (m, 2H), 2.70-2.56 (m, 2H), 1.36 (s, 3H),1.28 (s, 3H); LCMS m/z = 494.99 (M+; 20%).7-(2-((3aS,4R,6aR)-4-(4-Amino- 7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-chloro-6-fluoroquinolin- 2-amine

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-8- fluoroquinolin-2-amine LCMS m/z= 495.30 (M+; 70%). 7-(2-((3aS,4R,6aR)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)- 2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6- yl)ethyl)-3-chloro-8-fluoroquinolin- 2-amine

3,5-Dichloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)quinolin-2- amine LCMS m/z = 511.2(M+; 100%). 7-(2-((3aS,4R,6aR)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)- 2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6- yl)ethyl)-3,5-dichloroquinolin-2- amine

4-Chloro-7- ((3aS,4R,6aR)-2,2- dimethyl-6-(2-(3- methylimidazo[1,2-a]pyridin-7-yl)ethyl)- 3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3- d]pyrimidine ¹H NMR (400 MHz, DMSO-d6) δ 8.19 (d,J = 7.0 Hz, 1H), 8.04 (s, 1H), 7.43 (s, 1H), 7.31 (d, J = 1.1 Hz, 1H),6.98 (s, 2H), 6.91 (dd, J = 7.1, 1.7 Hz, 1H), 6.44 (d, J = 3.5 Hz, 1H),6.35 (d, J = 3.5 Hz, 1H), 5.55 (s, 1H), 5.50 (s, 1H), 5.32 (d, J = 5.6Hz, 1H), 4.38 (d, J = 5.7 Hz, 1H), 3.02-2.91 (m, 2H), 2.71- 2.57 (m,2H), 2.45 (d, J = 1.0 Hz, 3H), 1.38 (s, 3H), 1.28 (s, 3H); LCMS m/z =430.98 (M+; 30%).

4-chloro-7- ((3aS,4R,6aR)-6-(2-(3,3- dimethyl-2-(methylthio)-3H-indol-6-yl)ethyl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 4-yl)-7H-pyrrolo[2,3- d]pyrimidine ¹H NMR (400MHz, DMSO-d6) δ 9.42 (s, 2H), 8.06 (s, 1H), 7.32 (d, J = 7.6 Hz, 1H),7.10-6.95 (m, 4H), 6.45 (s, 2H), 5.56 (s, 1H), 5.51 (s, 1H), 5.28 (d, J= 5.6 Hz, 1H), 4.37 (d, J = 5.7 Hz, 1H), 3.02- 2.84 (m, 2H), 2.65-2.54(m, 2H), 1.46 (s, 6H), 1.36 (s, 3H), 1.28 (s, 3H); LCMS m/z = 459.36(M + 1; 20%). 7-((3aS,4R,6aR)-6-(2-(2-Amino-3,3-dimethyl-3H-indol-6-yl)ethyl)- 2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-amine

6′-(2-((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3] dioxol-6-yl)ethyl)-2′-(methylthio)spiro[cyclo- butane-1,3′-indole] ¹H NMR (400 MHz, DMSO-d6) δ8.06 (s, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.09-6.97 (m, 4H), 6.47- 6.40(m, 2H), 5.55 (s, 1H), 5.50 (s, 1H), 5.28 (d, J = 5.7 Hz, 1H), 4.37 (d,J = 5.6 Hz, 1H), 2.99-2.87 (m, 2H), 2.83-2.71 (m, 2H), 2.64- 2.53 (m,2H), 2.36-2.29 (m, 2H), 2.27-2.16 (m, 2H), 1.37 (s, 3H), 1.28 (s, 3H);LCMS m/z = 472.3 (M + 2; 100%). 6′-(2-((3aS,4R,6aR)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)- 2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6- yl)ethyl)spiro[cyclobutane-1,3′-indol]-2′-amine

7-(((3aS,4R,6aR)-4-(4- Chloro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3] dioxol-6-yl)methoxy)-N-methylquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.80(d, J = 8.9 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.15 (s, 1H), 7.06 (s,2H), 6.90 (dd, J = 8.6, 2.4 Hz, 1H), 6.86 (d, J = 3.6 Hz, 1H), 6.64 (d,J = 8.9 Hz, 1H), 6.52 (d, J = 3.6 Hz, 1H), 5.84 (s, 1H), 5.65 (s, 1H),5.42 (d, J = 5.6 Hz, 1H), 4.93 (s, 2H), 4.53 (d, J = 5.7 Hz, 1H), 2.93(d, J = 4.8 Hz, 3H), 1.46 (s, 3H), 1.30 (s, 3H); LCMS m/z = 459.40 (M +1; 30%).

3-Chloro-7- (((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol-6-yl)methoxy)-5- fluoro-N-(4- methoxybenzyl)quinolin- 2-amine ¹HNMR (400 MHz, DMSO-d6) δ 8.11 (s, 1H), 8.07 (s, 1H), 7.67 (t, J = 6.2Hz, 1H), 7.36-7.31 (m, 2H), 7.01 (s, 2H), 6.94 (d, J = 2.2 Hz, 1H),6.90-6.81 (m, 4H), 6.51 (d, J = 3.6 Hz, 1H), 5.83 (s, 1H), 5.65 (s, 1H),5.42 (d, J = 5.7 Hz, 1H), 4.94 (q, J = 15.3 Hz, 2H), 4.65 (d, J = 6.1Hz, 2H), 4.55 (d, J = 5.7 Hz, 1H), 3.70 (s, 3H), 1.43 (s, 3H), 1.29 (s,3H); LCMS m/z = 617.34 (M+; 100%). 7-(((3aS,4R,6aR)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6- yl)methoxy)-3-chloro-5-fluoro-N-(4-methoxybenzyl)quinolin-2-amine

N7-(((3aS,4R,6aR)-4-(4- Chloro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3] dioxol-6-yl)methyl)-N2-(4- methoxybenzyl)quinoline- 2,7-diamine LCMS m/z = 564.40 (M + 1;100%). N7-(((3aS,4R,6aR)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6- yl)methyl)-N2-(4-methoxybenzyl)quinoline-2,7- diamine

N7-(((3aS,4R,6aR)-4-(4- Chloro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)methyl)-N2-(4- methoxybenzyl)-N7- methylquinoline-2,7- diamine LCMSm/z = 576.95 (M − 1; 100%). N7-(((3aS,4R,6aR)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6- yl)methyl)-N2-(4-methoxybenzyl)-N7-methylquinoline-2,7-diamine

7-((((3aS,4R,6aR)-4-(4- Chloro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)methyl)thio)-N-(4- methoxybenzyl)quinolin- 2-amine ¹H NMR (400 MHz,DMSO-d6) δ 8.03 (s, 1H), 7.84 (d, J = 8.9 Hz, 1H), 7.57 (d, J = 8.3 Hz,1H), 7.49 (s, 2H), 7.36-7.26 (m, 2H), 7.18 (d, J = 8.4 Hz, 1H), 6.96 (s,2H), 6.84 (d, J = 8.2 Hz, 2H), 6.82- 6.76 (m, 1H), 6.16 (s, 1H), 6.01(s, 1H), 5.76 (s, 2H), 5.71 (s, 1H), 5.54 (s, 1H), 5.38 (s, 1H), 4.55(s, 1H), 4.34 (d, J = 5.5 Hz, 1H), 4.19 (d, J = 15.2 Hz, 1H), 3.70 (s,3H), 1.42 (s, 3H), 1.27 (s, 3H); LCMS m/z = 580.83 (M+; 100%).

3-Chloro-7- ((((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)methyl)thio)-N,N- bis(4-methoxybenzyl)quinolin- 2-amine LCMS m/z = 735.61 (M+; 80%).

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(2- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)quinolin-2- amine ¹H NMR (400 MHz,DMSO-d6) δ 8.43 (s, 1H), 8.17 (s, 1H), 7.61 (d, J = 8.3 Hz, 1H), 7.40(d, J = 1.5 Hz, 1H), 7.28 (s, 2H), 7.19 (dd, J = 8.3, 1.7 Hz, 1H), 6.69(s, 2H), 6.23 (d, J = 3.7 Hz, 1H), 6.03 (d, J = 3.6 Hz, 1H), 5.46 (s,1H), 5.43 (s, 1H), 5.33 (d, J = 5.7 Hz, 1H), 4.36 (d, J = 5.6 Hz, 1H),3.10- 2.93 (m, 2H), 2.67-2.56 (m, 2H), 1.36 (s, 3H), 1.28 (s, 3H); LCMSm/z = 476.98 (M+; 100%).

3-Bromo-7-(2- ((3aS,4R,6aR)-4-(4- chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-2,2-dimethyl-3a,6a- dihydro-4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-N-(4- methoxybenzyl)quinolin-2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.06 (s, 1H), 7.60 (d,J = 8.3 Hz, 1H), 7.45 (s, 1H), 7.36- 7.31 (m, 2H), 7.21-7.16 (m, 2H),6.95 (s, 2H), 6.86-6.82 (m, 2H), 6.35 (d, J = 2.1 Hz, 1H), 5.58 (s, 1H),5.48 (s, 1H), 5.28 (d, J = 5.6 Hz, 1H), 4.37 (d, J = 5.6 Hz, 1H), 4.27(d, J = 4.1 Hz, 2H), 3.68 (s, 3H), 3.05-2.97 (m, 2H), 2.67- 2.57 (m,2H), 1.36 (s, 3H), 1.27 (s, 3H); LCMS m/z = 660.97 (M + 1; 25%).

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)propyl)quinolin-2- amine Diastereomericmixture was separated by chiral preparative HPLC. Run Time (min): 10.00,Injection Volume: 5.00 μL Wavelength: 225 nm HEX_0.1% DEA_IPA_DCM_60_40_A_C_1.2 ML_10 MIN Flow Rate: 1.2 ml/min. Column: CHIRALPAK IACRL-027 OLD Column Temp: 25.0° C. Mobile Phase A: HEX_0.1% DEA MobilePhase C: IPA:DCMMobile Phase B: NA Mobile Phase D: NA Diastereomer-1 1HNMR (400 MHz, DMSO-d6) δ 8.17 (s, 1H), 8.04 (s, 1H), 7.61 (d, J = 8.2Hz, 1H), 7.38 (s, 1H), 7.16 (dd, J = 8.1, 1.6 Hz, 1H), 6.98 (s, 2H),6.67 (s, 2H), 6.32 (d, J = 3.5 Hz, 1H), 6.29 (d, J = 3.6 Hz, 1H), 5.55(s, 1H), 5.52 (s, 1H), 5.41 (d, J = 5.8 Hz, 1H), 4.35 (d, J = 5.8 Hz,1H), 3.12-3.03 (m, 1H), 2.96-2.90 (m, 1H), 2.88- 2.81 (m, 1H), 1.31 (s,3H), 1.27 (s, 3H), 1.17 (d, J = 6.8 Hz, 3H); LCMS m/z = 491.36 (M+;80%). Diastereomer-2 1H NMR (400 MHz, DMSO-d6) δ 8.17 (s, 1H), 8.06 (s,1H), 7.61 (d, J = 8.2 Hz, 1H), 7.36 (s, 1H), 7.15 (dd, J = 8.3, 1.6 Hz,1H), 6.97 (s, 2H), 6.67 (s, 2H), 6.56 (d, J = 3.6 Hz, 1H), 6.44 (d, J =3.6 Hz, 1H), 5.60-5.56 (m, 1H), 5.52 (d, J = 2.5 Hz, 1H), 5.34 (d, J =5.7 Hz, 1H), 4.40 (d, J = 5.7 Hz, 1H), 3.13-3.04 (m, 1H), 2.93 (q, J =7.2 Hz, 1H), 2.83 (d, J = 10.0 Hz, 1H), 1.40 (s, 3H), 1.28 (s, 3H), 1.14(d, J = 6.8 Hz, 3H); LCMS m/z = 491.36 (M+; 80%).

3-Bromo-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)propyl)-N-(4- methoxybenzyl)quinolin-2-amine Diastereomeric mixture was separated by chiral preparative HPLC.Run Time (min): 10.00 Injection Volume: 5.00 μL, Wavelength: 251 nm,HEX_0.1% DEA_IPA- DCM_50_50_A_C_1.0 ML_10 MIN_251 nm Flow Rate: 1.0ml/min. Column: CHIRALPAK IG CRL-071 Column Temp: 25.0° C. Mobile PhaseA: HEX_0.1% DEA Mobile Phase C: IPA-DCM_1-1, Mobile Phase B: NA MobilePhase D: NA Diastereomer-1: ¹H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1H),8.07 (s, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.41 (d, J = 1.4 Hz, 1H), 7.37-7.33 (m, 2H), 7.19-7.13 (m, 2H), 6.99 (s, 2H), 6.87-6.83 (m, 2H), 6.63(d, J = 3.6 Hz, 1H), 6.46 (d, J = 3.5 Hz, 1H), 5.59 (s, 1H), 5.53 (s,1H), 5.32 (d, J = 5.7 Hz, 1H), 4.65 (d, J = 6.0 Hz, 2H), 4.40 (d, J =5.8 Hz, 1H), 3.69 (s, 3H), 3.11-3.04 (m, 1H), 2.86-2.76 (m, 2H), 1.41(s, 3H), 1.28 (s, 3H), 1.14 (d, J = 6.5 Hz, 3H); LCMS m/z = 657.47 (M +2; 45%). Diastereomer-2: ¹H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.05(s, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.42 (s, 1H), 7.33 (d, J = 8.5 Hz,2H), 7.18-7.13 (m, 2H), 7.00 (s, 2H), 6.84 (d, J = 8.6 Hz, 2H), 6.43 (d,J = 3.6 Hz, 1H), 6.38 (d, J = 3.5 Hz, 1H), 5.55 (s, 1H), 5.52 (s, 1H),5.42 (d, J = 5.7 Hz, 1H), 4.63 (d, J = 6.0 Hz, 2H), 4.38 (d, J = 5.7 Hz,1H), 3.69 (s, 3H), 3.10- 3.05 (m, 1H), 2.96-2.90 (m, 2H), 1.32 (s, 3H),1.27 (s, 3H), 1.16 (d, J = 6.8 Hz, 3H); LCMS m/z = 655.47 (M+; 35%).

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)propyl)-5- fluoroquinolin-2-amine LCMSm/z = 509.3 (M+; 60%). 7-(2-((3aS,4R,6aR)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)- 2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6- yl)propyl)-3-chloro-5-fluoroquinolin-2-amine

Diastereomeric mixture was separated by chiral preparative HPLC. RunTime (min): 15.00, Injection Volume: 10.00 μL, Wavelength: 254 nm, FlowRate: 1.50 ml/min, Column Temp: 30.0° C., Instrument Method:ACN_DEA_100_B_1.5 ML_15 MIN_254 NM, Column: CHIRALPAK OX-H CRL-061,Mobile Phase A: NA, Mobile Phase B: ACN_0.1% DEA Diastereomer-1: LCMSm/z = 553.20, 555.20 (M+; M + 2; 100%) Diastereomer-2: ¹H NMR (400 MHz,DMSO-d6) δ 8.35 (s, 1H), 8.06 (s, 1H), 7.20 (s, 1H), 7.00- 6.96 (m, 3H),6.86 (s, 2H), 6.57 (d, J = 3.5 Hz, 1H), 6.45 (d, J = 3.5 Hz, 1H), 5.57(s, 1H), 5.53 (s, 1H), 5.34 (d, J = 5.8 Hz, 1H), 4.41 (d, J = 5.7 Hz,1H), 3.09-3.01 (m, 2H), 2.85-2.83 (m, 1H), 1.40 (s, 3H), 1.28 (s, 3H),1.15 (d, J = 6.0 Hz, 3H); LCMS m/z = 555.20 (M + 2; 100%)

7-(1-((3aS,4R,6aR)-4-(4- Chloro-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol- 6-yl)ethoxy)-N-methylquinolin-2-amine LCMS m/z = 473.11 (M + 1; 20%).7-(1-((3aS,4R,6aR)-4-(4-Amino- 7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethoxy)-N-methylquinolin-2- amine

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,6a- trimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR(400 MHz, DMSO-d6) δ 8.17 (d, J = 0.7 Hz, 1H), 8.09 (s, 1H), 7.27 (s,1H), 7.09-7.01 (m, 3H), 6.95 (s, 2H), 6.65 (d, J = 3.5 Hz, 1H), 6.47 (d,J = 3.5 Hz, 1H), 5.63-5.58 (m, 1H), 5.49-5.44 (m, 1H), 4.00 (d, J = 0.9Hz, 1H), 3.06 (t, J = 7.6 Hz, 2H), 2.70- 2.59 (m, 1H), 2.59-2.53 (m,1H), 1.39 (s, 3H), 1.30 (s, 3H), 1.28 (s, 3H); LCMS m/z = 509.2 (M+;90%). 7-(2-((3aS,4R,6aR)-4-(4-Amino- 7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,6a-trimethyl-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-chloro-5-fluoroquinolin- 2-amine

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-6a- ethyl-2,2-dimethyl-3a,6a- dihydro-4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR(400 MHz, DMSO-d6) δ 8.18 (s, 1H), 8.09 (s, 1H), 7.28 (s, 1H), 7.06 (dd,J = 11.1, 1.4 Hz, 1H), 6.99 (s, 2H), 6.95 (s, 2H), 6.68 (d, J = 3.5 Hz,1H), 6.45 (d, J = 3.5 Hz, 1H), 5.73 (d, J = 2.3 Hz, 1H), 5.47-5.43 (m,1H), 4.09 (s, 1H), 3.07 (t, J = 7.6 Hz, 2H), 2.70- 2.54 (m, 2H), 1.84(dq, J = 14.9, 7.4 Hz, 1H), 1.59 (dq, J = 14.7, 7.4 Hz, 1H), 1.31 (s,3H), 1.27 (s, 3H), 0.68 (t, J = 7.4 Hz, 3H); LCMS m/z = 523.44 (M+;95%).

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,6a- trimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)propyl)-5- fluoroquinolin-2-amineDiastereomer-1: ¹H NMR (400 MHz, DMSO-d6) δ 8.20 (s, 1H), 8.06 (s, 1H),7.26 (s, 1H), 7.06 (dd, J = 11.1, 1.4 Hz, 1H), 6.96(s, 4H), 6.21 (d, J =3.5 Hz, 1H), 5.97 (d, J = 3.6 Hz, 1H), 5.69 (d, J = 2.6 Hz, 1H), 5.45(d, J = 2.7 Hz, 1H), 3.86 (s, 1H), 3.10-2.97 (m, 2H), 2.93-2.84 (m, 1H),1.36 (s, 3H), 1.27 (s, 3H), 1.24 (d, J = 3.0 Hz, 3H), 1.19 (s, 3H); LCMSm/z = 523.32 (M+; 50%). Note-Only desired isomer was isolated

3-Chloro-7- (((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,6a- trimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)methoxy)-5-fluoro- N-(4-methoxybenzyl)quinolin- 2-amine LCMS m/z = 631.30 (M+; 60%).7-(((3aS,4R,6aR)-4-(4-Amino-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2,6a-trimethyl-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)methoxy)-3-chloro-5-fluoro-N- (4-methoxybenzyl)quinolin-2-amine

3-Chloro-7-(1- ((3aS,4R,6aR)-4-(4- chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethoxy)-5-fluoro-N- (4-methoxybenzyl)quinolin- 2-amine Diastereomer-1 LCMS m/z = 631.34 (M+;100%). Diastereomer-2 LCMS m/z = 631.34 (M+; 100%).7-(1-((3aS,4R,6aR)-4-(4-Amino- 7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethoxy)-3-chloro-5-fluoro-N-(4- methoxybenzyl)quinolin-2-amine

3-bromo-7-(2- ((3aR,3bR,4aS,5R,5aS)- 5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-2,2- dimethylhexahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b- yl)ethyl)-N-(4-methoxybenzyl)quinolin- 2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.33 (s,1H), 8.08 (s, 1H), 7.57 (d, J = 8.2 Hz, 1H), 7.43 (d, J = 1.6 Hz, 1H),7.37-7.31 (m, 2H), 7.19 (t, J = 6.1 Hz, 1H), 7.16 (dd, J = 8.2, 1.6 Hz,1H), 7.14 (d, J = 3.5 Hz, 1H), 7.03 (s, 2H), 6.90- 6.84 (m, 2H), 6.61(d, J = 3.5 Hz, 1H), 5.21 (d, J = 7.3 Hz, 1H), 5.01 (s, 1H), 4.62 (d, J= 6.1 Hz, 2H), 4.51 (dd, J = 7.4, 1.5 Hz, 1H), 3.71 (s, 3H), 2.88-2.79(m, 2H), 2.36-2.24 (m, 1H), 1.67- 1.58 (m, 1H), 1.48 (s, 3H), 1.46- 1.41(m, 1H), 1.19 (s, 3H), 0.92 (t, J = 4.7 Hz, 1H), 0.74-0.68 (m, 1H); LCMSm/z = 656.2 (M + 1; 40%).

3-bromo-7-((E)-1- ((3aR,3bS,4aS,5R,5aS)- 5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)prop-1-en-2-yl)-N-(4- methoxybenzyl)quinolin- 2-amine ¹H NMR (400MHz, DMSO-d6) δ 8.38 (s, 1H), 8.08 (s, 1H), 7.64 (s, 1H), 7.58 (d, J =8.3 Hz, 1H), 7.45-7.40 (m, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.16 (d, J =3.6 Hz, 1H), 7.12 (t, J = 6.0 Hz, 1H), 7.01 (s, 2H), 6.87 (d, J = 8.6Hz, 2H), 6.63 (d, J = 3.5 Hz, 1H), 6.17 (s, 1H), 5.26 (d, J = 6.9 Hz,1H), 4.94 (s, 1H), 4.70 (dd, J = 14.7, 6.0 Hz, 1H), 4.59 (dd, J = 14.7,6.0 Hz, 1H), 4.48 (d, J = 6.9 Hz, 1H), 3.71 (s, 3H), 2.12 (s, 3H), 1.51(s, 3H), 1.46-1.39(m, 1H), 1.19 (s, 3H), 0.90 (t, J = 5.1 Hz, 1H),0.26-0.18 (m, 1H); LCMS m/z = 668.97 (M + 1; 30%).

3-chloro-7-(2- ((3aR,3bS,4aS,5R,5aS)- 5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)propyl)-5-fluoro-N-(4- methoxybenzyl)quinolin- 2-amine Diastereomericmixture was separated by chiral preparative HPLC. Wavelength: 225 nm,Instrument Method: HEX-0.1% DEA_IPA- DCM_50_50_ A_C_1.2 ML_8 MIN FlowRate: 1.2 ml/min, Column: CHIRALPAK IG CRL-071 Column Temp: 25° C.,Mobile Phase A: HEX_0.1% DEA Mobile Phase C: IPA-DCM, Mobile Phase B: NAMobile Phase D: NA First Diastereomer: LCMS m/z = 643.09(M+; 30%).Second Diastereomer: LCMS m/z = 643.09(M+; 30%).

3-chloro-7-(2- ((3aR,3bS,4aS,5R,5aS)- 5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)-2-cyclopropylethyl)- 5-fluoro-N-(4- methoxybenzyl)quinolin- 2-amineLCMS m/z = 669.10(M+; 20%). 7-(2-((3aR,3bS,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4] cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)-2-cyclopropylethyl)-3- chloro-5-fluoro-N-(4-methoxybenzyl)quinolin-2-amine

3-Bromo-7-(2- ((3aR,3bS,4aS,5R,5aS)- 5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)- yl)propyl)-N-(4-methoxybenzyl)quinolin- 2-amine LCMS m/z = 670.97(M + 1; 20%).

7-(2- ((3aR,3bR,4aS,5R,5aS)- 5-(4-chloro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)- yl)ethyl)-N-(4- methoxybenzyl)quinazolin- 2-amine¹H NMR (400 MHz, DMSO-d6) δ 9.04 (s, 1H), 8.07 (s, 1H), 7.79 (t, J = 6.3Hz, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.35 (s, 1H), 7.30 (d, J = 8.2 Hz,2H), 7.17 (dd, J = 8.2, 1.6 Hz, 1H), 7.13 (d, J = 3.5 Hz, 1H), 7.01 (s,2H), 6.90-6.84 (m, 2H), 6.61 (d, J = 3.5 Hz, 1H), 5.21 (d, J = 7.1 Hz,1H), 5.01 (s, 1H), 4.57-4.48 (m, 3H), 3.71 (s, 3H), 2.91-2.80 (m, 2H),2.35- 2.24 (m, 1H), 1.69-1.58 (m, 1H), 1.48 (s, 3H), 1.47-1.42 (m, 1H),1.20 (s, 3H), 0.93 (t, J = 4.7 Hz, 1H), 0.75-0.69 (m, 1H); LCMS m/z =578.3 (M + 1; 90%).

7-(2- ((3aR,3bR,4aS,5R,5aS)- 5-(4-Chloro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)- yl)ethyl)-8- fluoroquinolin-2-amine ¹H NMR (400MHz, DMSO-d6) δ 8.07 (s, 1H), 7.88 (d, J = 8.9 Hz, 1H), 7.36 (d, J = 8.2Hz, 1H), 7.13 (d, J = 3.7 Hz, 1H), 7.09 (t, J = 7.4 Hz, 1H), 7.00 (s,2H), 6.75 (d, J = 8.9 Hz, 1H), 6.65 (s, 2H), 6.61 (d, J = 3.5 Hz, 1H),5.21 (d, J = 7.2 Hz, 1H), 5.01 (s, 1H), 4.55 (d, J = 7.2 Hz, 1H),2.93-2.79 (m, 2H), 2.29-2.20 (m, 1H), 1.68-1.58 (m, 1H), 1.49 (s, 3H),1.47-1.43 (m, 1H), 1.21 (s, 3H), 0.96 (t, J = 4.8 Hz, 1H), 0.75 (dd, J =9.0, 5.0 Hz, 1H); LCMS m/z = 475.2 (M + 1; 30%).

7-(2- ((3aR,3bR,4aS,5R,5aS)- 5-(4-chloro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethylhexahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b- yl)ethyl)-N- methylquinolin-2-amine ¹H NMR (400 MHz,DMSO-d6) δ 8.08 (s, 1H), 7.84 (d, J = 8.9 Hz, 1H), 7.55 (d, J = 8.1 Hz,1H), 7.46 (s, 1H), 7.16-7.10 (m, 2H), 7.06 (s, 2H), 6.72 (d, J = 8.9 Hz,1H), 6.62 (d, J = 3.5 Hz, 1H), 5.22 (d, J = 7.2 Hz, 1H), 5.02 (s, 1H),4.52 (dd, J = 7.3, 1.5 Hz, 1H), 2.91 (d, J = 4.7 Hz, 3H), 2.88-2.77 (m,2H), 2.32-2.24 (m, 1H), 1.70-1.61 (m, 1H), 1.49 (s, 3H), 1.48-1.44 (m,1H), 1.20 (s, 3H), 0.94 (t, J = 4.7 Hz, 1H), 0.74 (dd, J = 9.2, 5.0 Hz,1H); LCMS m/z = 471.23 (M + 1; 15%).

3-bromo-7- (((3aR,3bR,4aS,5R,5aS)- 5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)- yl)methoxy)-N-(4-methoxybenzyl)quinolin- 2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.30 (s,1H), 8.09 (s, 1H), 7.64- 7.59 (m, 1H), 7.38 (d, J = 3.6 Hz, 1H),7.37-7.31 (m, 2H), 7.16 (t, J = 5.9 Hz, 1H), 7.04 (s, 2H), 7.00 (d, J =2.5 Hz, 1H), 6.97-6.92 (m, 1H), 6.91-6.84 (m, 2H), 6.65 (d, J = 3.6 Hz,1H), 5.30 (d, J = 7.1 Hz, 1H), 5.14 (s, 1H), 4.63 (d, J = 6.0 Hz, 2H),4.50 (d, J = 7.1 Hz, 1H), 4.35 (d, J = 10.5 Hz, 1H), 4.21 (d, J = 10.5Hz, 1H), 3.71 (s, 3H), 1.78- 1.71 (m, 1H), 1.48 (s, 3H), 1.18 (s, 3H),1.11-1.06 (m, 1H), 0.88- 0.83 (m, 1H); LCMS m/z = 659.3 (M + 2; 100%).

7- ((((3aR,3bS,4aS,5R,5aS)- 5-(4-chloro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)- yl)methyl)thio)-N-(4- methoxybenzyl)quinolin-2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.80 (d, J = 8.9 Hz,1H), 7.53 (d, J = 8.4 Hz, 1H), 7.46 (t, J = 5.7 Hz, 1H), 7.41 (d, J =1.8 Hz, 1H), 7.35-7.30 (m, 2H), 7.23 (d, J = 3.5 Hz, 1H), 7.12 (dd, J =8.3, 1.9 Hz, 1H), 7.01 (s, 2H), 6.91-6.86 (m, 2H), 6.75 (d, J = 8.9 Hz,1H), 6.58 (d, J = 3.5 Hz, 1H), 5.23 (dd, J = 7.3, 1.4 Hz, 1H), 5.03 (s,1H), 4.55 (d, J = 5.7 Hz, 2H), 4.51 (dd, J = 7.4, 1.5 Hz, 1H), 3.72 (s,3H), 3.67 (d, J = 12.6 Hz, 1H), 3.32 (d, J = 12.7 Hz, 1H), 1.71-1.63 (m,1H), 1.47 (s, 3H), 1.17 (s, 3H), 1.06 (t, J = 4.8 Hz, 1H), 1.01- 0.95(m, 1H); LCMS m/z = 595.21 (M+; 70%)

7- ((3aR,3bR,4aS,5R,5aS)- 3b-(2-(3,3-dimethyl-2-(methylthio)-3H-indol-6- yl)ethyl)-2,2- dimethylhexahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3]dioxol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin- 4-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.07 (s,1H), 7.18 (d, J = 7.5 Hz, 1H), 7.11 (d, J = 3.6 Hz, 1H), 7.01 (s, 2H),6.94 (s, 1H), 6.88 (d, J = 7.6 Hz, 1H), 6.61 (d, J = 3.5 Hz, 1H), 5.18(d, J = 7.2 Hz, 1H), 5.00 (s, 1H), 4.52 (d, J = 7.1 Hz, 1H), 2.77-2.65(m, 2H), 2.22-2.12 (m, 1H), 1.66-1.55 (m, 1H), 1.47 (s, 3H), 1.44 (dd, J= 9.2, 4.3 Hz, 1H), 1.36 (s, 3H), 1.24 (s, 3H), 1.19 (s, 3H), 0.93 (t, J= 4.7 Hz, 1H), 0.75 (dd, J = 9.1, 5.0 Hz, 1H); LCMS m/z = 473.4 (M + 1;80%)

7-(2- ((3aR,3bR,4aS,5R,5aS)- 5-(4-chloro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethylhexahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b- yl)ethyl)-N-(4- methoxybenzyl)quinolin- 2-amine ¹H NMR(400 MHz, Chloroform-d) δ 8.34 (s, 1H), 7.87 (d, J = 8.9 Hz, 1H), 7.63(s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.5 Hz, 2H), 7.22 (d, J= 8.1 Hz, 1H), 6.97 (d, J = 3.6 Hz, 1H), 6.91 (d, J = 8.7 Hz, 2H), 6.65(d, J = 9.0 Hz, 1H), 6.39 (d, J = 3.6 Hz, 1H), 5.25 (s, 2H), 5.19 (d, J= 7.1 Hz, 1H), 5.14 (s, 1H), 4.67-4.62 (m, 3H), 3.82 (s, 3H), 3.06-2.93(m, 2H), 2.41- 2.36 (m, 1H), 2.06-2.01 (m, 1H), 1.60 (s, 3H), 1.51 (dd,J = 8.7, 4.2 Hz, 1H), 1.28 (s, 3H), 1.15 (t, J = 4.8 Hz, 1H), 0.78 (dd,J = 5.5, 3.2 Hz, 1H); LCMS m/z = 577.5 (M + 1; 60%)

7-(1-3aR,3bR,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)propan-2-yl)-N-(4-methoxybenzyl)quinolin-2-amine

A mixture of7-((E)-1-((3aR,3bS,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)prop-1-en-2-yl)-3-bromo-N-(4-methoxybenzyl)quinolin-2-amine(0.05 g, 0.075 mmol), ammonium formate (0.331 g, 5.24 mmol) and Pd/C(0.024 g, 0.225 mmol) in EtOH (15 ml) was heated at 75° C. for 8 h. Thereaction mixture was cooled 25° C., filtered through celite andconcentrated in vacuo to get 0.06 g of crude compound. The obtainedresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution (0 to 5%) of methanolin dichloromethane to afford the title compound (0.042 g, 95%) as anoff-white solid. LCMS m/z=591.29 (M+1, 100%).

EXAMPLES Example-1:(1S,2R5R)-3-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7Hpyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol (Compound-1)

The mixture of7-(2-((3aS,4R,6aR)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-bromo-N-(4-methoxybenzyl)quinolin-2-amine (0.220 g, 0.343 mmol) in TFA (3.96 ml, 51.4mmol) was stirred at 50° C. for 1.5 h. The resulting mixture wasconcentrated in vacuo and obtained residue was dissolved in MeOH (5 ml).K₂CO₃ (0.142 g, 1.029 mmol) was added and stirred the reaction mixtureat 50° C. for 1.5 h. Reaction mixture was filtered and filtrate wasconcentrated under reduced pressure to get 0.27 g of crude compound.This residue was purified by combiflash (R_(f)200, Teledyne/Isco)instrument onto a Redisep® R_(f) column with gradient elution (0 to 7%)of methanol in dichloromethane to afford the title compound (0.03 g,18%) as an off-white solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H),8.06 (s, 1H), 7.61 (d, J=8.2 Hz, 1H), 7.36 (d, J=1.6 Hz, 1H), 7.16 (dd,J=8.2, 1.7 Hz, 1H), 7.08 (s, 2H), 6.67 (d, J=3.5 Hz, 1H), 6.61 (s, 2H),6.45 (d, J=3.5 Hz, 1H), 5.50 (d, J=4.4 Hz, 1H), 5.44 (t, J=1.7 Hz, 1H),4.98 (d, J=6.4 Hz, 2H), 4.45 (t, J=5.9 Hz, 1H), 3.97 (d, J=5.0 Hz, 1H),3.04-2.87 (m, 2H), 2.61-2.53 (m, 2H); LCMS m/z=483.01 (M+2, 90%).

Examples in table-13 were synthesized by following an analogous reactionprotocol as was used for the preparation of(1S,2R,5R)-3-(2-(2-amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diolusing the appropriate starting materials (Instead of TFA, 3N HCl/MeOHcould also be used).

TABLE 13 Structure & IUPAC name Intermediate used ¹H NMR & LCMS data

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl- 3a,6a-dihydro-4H- cyclopenta[d][l,3]dioxol-6-yl)ethyl)-3-chloro-N- (4- methoxybenzyl)quinolin- 2-amine ¹H NMR (400MHz, DMSO-d6) δ 8.17 (s, 1H), 8.09 (s, 1H), 7.61 (d, J = 8.2 Hz, 1H),7.37 (s, 1H), 7.29 (s, 2H), 7.16 (dd, J = 8.3, 1.7 Hz, 1H), 6.75-6.66(m, 3H), 6.49 (d, J = 3.6 Hz, 1H), 5.50 (d, J = 4.4 Hz, 1H), 5.43 (d, J= 1.9 Hz, 1H), 5.01 (d, J = 6.7 Hz, 2H), 4.45 (t, J = 5.9 Hz, 1H), 3.96(d, J = 5.0 Hz, 1H), 2.94 (ddt, J = 21.4, 14.1, 7.2 Hz, 2H), 2.58-2.55(m, 2H); LCMS m/z = 436.92 (M+, 20%)

7-(2-((3aS,4R,6aR)-4- (4-amino-5-fluoro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl- 3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-bromo-N- (4- methoxybenzyl)quinolin- 2-amine ¹H NMR (400MHz, DMSO-d6) δ 8.39 (s, 1H), 8.08 (s, 1H), 7.63 (d, J = 8.2 Hz, 1H),7.37 (s, 1H), 7.18 (dd, J = 8.2, 1.6 Hz, 3H), 6.72 (d, J = 27.4 Hz, 2H),6.55 (d, J = 2.1 Hz, 1H), 5.54 (s, 1H), 5.40 (q, J = 1.7 Hz, 1H),5.10-4.91 (m, 2H), 4.43 (d, J = 5.7 Hz, 1H), 3.92 (q, J = 5.2 Hz, 1H),3.04-2.87 (m, 2H) 2.65-2.52 (m, 2H),; LCMS m/z = 501 (M + 1, 30%)

7-((((3aS,4R,6aR)-4-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)methyl)thio)-N-(4- methoxybenzyl)quinolin- 2-amine ¹H NMR (400 MHz,DMSO-d6) δ 8.00 (s, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 8.3 Hz,1H), 7.40 (d, J = 1.8 Hz, 1H), 7.15 (dd, J = 8.3, 1.9 Hz, 1H), 6.89 (s,2H), 6.72 (d, J = 8.8 Hz, 1H), 6.48 (s, 2H), 6.26 (d, J = 3.5 Hz, 1H),6.21 (d, J = 3.6 Hz, 1H), 5.57 (s, 1H), 5.49 (s, 1H), 5.11 (d, J = 5.5Hz, 1H), 5.04 (d, J = 6.4 Hz, 1H), 4.58 (s, 1H), 4.01 (d, J = 14.7 Hz,1H), 3.88-3.81 (m, 1H), 3.75-3.66 (m, 1H); LCMS m/z = 420.85 (M+, 100%)

7-((((3aS,4R,6aR)-4-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)methyl)thio)-3- chloro-N,N-bis(4- methoxybenzyl)quinolin- 2-amine¹H NMR (400 MHz, DMSO-d6) δ 8.19 (s, 1H), 8.00 (s, 1H), 7.62 (d, J = 8.4Hz, 1H), 7.43 (s, 1H), 7.23 (dd, J = 8.4, 1.9 Hz, 1H), 6.94 (s, 2H),6.82 (s, 2H), 6.28 (q, J = 3.5 Hz, 2H), 5.61 (s, 1H), 5.50 (s, 1H), 5.09(dd, J = 24.6, 6.5 Hz, 2H), 4.57 (t, J = 6.0 Hz, 1H), 4.04 (d, J = 14.9Hz, 1H), 3.87 (q, J = 5.7 Hz, 1H), 3.74 (d, J = 15.0 Hz, 1H); LCMS m/z =455.50 (M+, 50%)

N7-(((3aS,4R,6aR)-4-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)methyl)-N2-(4- methoxybenzyl)-N7- methylquinoline-2,7- diamine ¹HNMR (400 MHz, DMSO-d6) δ 8.02 (s, 1H), 7.65 (d, J = 8.7 Hz, 1H), 7.39(d, J = 8.8 Hz, 1H), 6.95- 6.86 (m, 3H), 6.81 (dd, J = 8.9, 2.6 Hz, 1H),6.61 (d, J = 2.5 Hz, 1H), 6.49 (d, J = 3.5 Hz, 1H), 6.41 (d, J = 8.7 Hz,1H), 6.09 (s, 2H), 5.51 (s, 1H), 5.41 (d, J = 1.9 Hz, 1H), 5.06 (dd, J =6.5,2.5 Hz, 2H), 4.44 (t, J = 6.0Hz, 1H), 4.17 (d, J = 4.9 Hz, 2H),4.11-4.04 (m, 1H), 3.05 (s, 3H); LCMS m/z = 417.10 (M+, 100%)

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl- 3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)propyl)-3-bromo- N-(4-methoxybenzyl) quinolin-2-amine FirstDiastereomer (Compound- 7a): ¹H NMR (400 MHz, DMSO- d6) δ 8.35 (s, 1H),8.05 (s, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.33 (s, 1H), 7.13 (d, J = 8.4Hz, 1H), 6.93 (s, 2H), 6.78 (d, J = 3.6 Hz, 1H), 6.59 (s, 2H), 6.49 (d,J = 3.6 Hz, 1H), 5.53 (d, J = 4.5 Hz, 1H), 5.42 (s, 1H), 5.01-4.88 (m,2H), 4.46 (t, J = 5.8 Hz, 1H), 3.99 (t, J = 7.8 Hz, 1H), 3.03 (dd, J =11.9, 4.4 Hz, 1H), 2.73 (q, J = 10.6, 8.9 Hz, 2H), 1.24 (s, 3H); LCMSm/z = 497.30 (M + 2, 100%) Second Diastereomer (Compound- 7b): ¹H NMR(400 MHz, DMSO- d6) δ 8.36 (s, 1H), 8.05 (s, 1H), 7.61 (d, J = 8.2 Hz,1H), 7.33 (s, 1H), 7.21-7.02 (m, 3H), 6.61 (s, 2H), 6.50 (d, J = 3.5 Hz,1H), 6.43 (d, J = 3.6 Hz, 1H), 5.52 (d, J = 5.0 Hz, 1H), 5.35 (s, 1H),5.00 (s, 1H), 4.91 (d, J = 6.4 Hz, 1H), 4.56 (s, 1H), 3.90 (d, J = 5.8Hz, 1H), 3.07- 2.99 (m, 1H), 2.83-2.74 (m, 2H) 1.09 (d, J = 5.8 Hz, 3H);LCMS m/z = 495.24 (M+, 40%)

7-(1-((3aS,4R,6aR)-4-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3] dioxol-6-yl)ethoxy)-N-methyl quinolin-2-amine Diastereomeric mixture was separated by chiralpreparative HPLC. Wavelength: 225 nm, Instrument Method: IPA_0.1%DEA_MeOH_ 0.1% DEA_50_50_0.7ML_12MIN, Flow Rate: 0.70 ml/min Column:CHIRALPAK IB CRL-043 OLD, Column Temp: 30° C., Mobile Phase A: IPA_0.1%DEA, Mobile Phase B: MeOH_0.1% DEA First Diastereomer (Compound- 8a): ¹HNMR (400 MHz, DMSO-d6) δ 8.04 (s, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.49(d. J = 8.7 Hz, 1H), 7.00 (d, J = 2.5 Hz, 1H), 6.92 (d, J = 4.2 Hz, 2H),6.84-6.80 (m, 2H), 6.57 (d, J = 8.8 Hz, 1H), 6.44 (d, J = 3.5 Hz, 1H),5.70 (t, J = 1.7 Hz, 1H), 5.60-5.56 (m, 1H), 5.21 (d, J = 6.7 Hz, 1H),5.14-5.08 (m, 1H), 5.04-4.99 (m, 1H), 4.62- 4.58 (m, 1H), 4.15-4.11 (m,1H), 3.19-3.16 (m, 1H), 2.90 (d, J = 4.7 Hz, 3H), 1.54 (d, J = 6.3 Hz,3H); LCMS m/z = 433.04 (M + 1, 30%) Second Diastereomer (Compound-8b):¹H NMR (400 MHz, DMSO-d6) δ 8.02 (s, 1H), 7.73 (d, J = 8.9 Hz, 1H), 7.49(d, J = 8.7 Hz, 1H), 7.04 (d, J = 2.5Hz, 1H), 6.94 (d, J = 3.5 Hz, 3H),6.81 (dd, J = 8.7, 2.5 Hz, 1H), 6.57 (d, J = 8.8 Hz, 1H), 6.54 (d, J =3.6 Hz, 1H), 5.72 (t, J = 1.5 Hz, 1H), 5.57 (d, J = 5.0 Hz, 1H), 5.26(d, J = 6.7 Hz, 1H), 5.15 (s, 1H), 5.10 (s, 1H), 4.48 (s, 1H), 4.36 (d,J = 4.2 Hz, 1H), 3.94 (d, J = 5.8 Hz, 1H), 2.91 (d, J = 4.7 Hz, 3H),1.57 (d, J = 6.5 Hz, 3H); LCMS (m/z) = 433.04 (M+, 30%).

7-(((3aS,4R,6aR)-4-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2,6a-trimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)methoxy)-3-chloro-5- fluoro-N-(4- methoxybenzyl)quinolin- 2-amine¹H NMR (400 MHz, DMSO- d6) δ 8.37 (s, 1H), 8.14 (s, 1H), 7.71 (d, J =3.7 Hz, 1H), 7.07 (s, 2H), 6.97 (d, J = 3.6 Hz, 1H), 6.90 (d, J = 2.2Hz, 1H), 6.79 (dd, J = 11.5, 2.2 Hz, 1H), 5.61 (s, 2H), 4.89-4.77 (m,2H), 4.76-4.63 (m, 3H), 1.82 (s, 3H); LCMS m/z = 471.07 (M+, 100%)

7-(2-((3aS,4R,6aR)-4-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-N-methylquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.03 (s, 1H), 7.79(d, J = 8.9 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.39 (s, 1H), 7.07 (dd, J= 8.1, 1.6 Hz, 1H), 6.93 (s, 2H), 6.72-6.64 (m,2H), 6.41 (d, J = 3.5 Hz,1H), 5.51 (s, 1H), 5.43 (d, J = 1.9 Hz, 1H), 4.95 (dd, J = 10.7, 6.5 Hz,2H), 4.45 (t, J = 6.0 Hz, 1H), 4.01-3.90 (m, 1H), 3.12-3.08 (m, 2H),2.90 (d, J = 4.7 Hz, 3H), 2.60-2.52 (m, 2H); LCMS m/z = 416.48 (M+, 60%)

7-((3aS,4R,6aR)-2,2- dimethyl-6-(2-(3- methylimidazo[1,2-a]pyridin-7-yl)ethyl)- 3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-amine ¹H NMR (400 MHz, DMSO-d6) δ8.20 (d, J = 7.0 Hz, 1H), 8.03 (s, 1H), 7.39 (s, 1H), 7.32 (s, 1H),7.00-6.86 (m, 3H), 6.66 (d, J = 3.5 Hz, 1H), 6.42 (d, J = 3.5 Hz, 1H),5.53-5.41 (m, 2H), 4.98 (d, J = 6.4 Hz, 2H), 4.46 (t, J = 6.0 Hz, 1H),3.98 (q, J = 5.5 Hz, 1H), 3.40 (d, J = 7.0 Hz, 2H), 2.99-2.82 (m, 2H),2.45 (s, 3H); LCMS m/z = 390.91 (M+, 90%)

3-chloro-5-fluoro-N-(4- methoxybenzyl)-7- (((3aS,4R,6aR)-4-(4-((4-methoxybenzyl)amino)- 7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2,5-trimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)methoxy)quinolin-2- amine LCMS m/z = 471.23 (M+, 60%)

3-chloro-7-(2- ((3aS,4R,6aR)-2,2- dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR(400 MHz, DMSO-d6) δ 8.62 (s, 1H), 8.18 (s, 1H), 7.22 (s, 1H), 7.13-6.90(m, 4H), 6.55 (d, J = 3.6 Hz, 1H), 5.61 (d, J = 4.4 Hz, 1H), 5.46 (t, J= 1.7 Hz, 1H), 5.02 (dd, J = 6.5, 4.3 Hz, 2H), 4.47 (t, J = 6.0 Hz, 1H),4.08-3.98 (m, 1H), 3.04-2.85 (m, 2H), 2.63 (s, 3H), 2.60- 2.54 (m, 2H);LCMS m/z = 454.17 (M+, 100%)

3-chloro-7-(2- ((3aS,4R,6aR)-2,2- dimethyl-4-(4-methyl-1H-pyrrolo[3,2-c]pyridin-1- yl)-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO- d6) δ 14.95(s, 1H), 8.41 (s, 1H), 8.26 (t, J = 5.9 Hz, 1H), 7.94 (d, J = 6.9 Hz,1H), 7.53 (d, J = 3.5 Hz, 1H), 7.43-7.29 (m, 2H), 7.29-7.03 (m, 3H),5.64 (s, 1H), 5.58 (d, J = 5.3 Hz, 1H), 4.41 (d, J = 5.6 Hz, 1H), 3.88(t, J = 5.6 Hz, 1H), 3.10-2.99 (m, 2H)), 2.93 (s, 3H), 2.62-2.50 (m,2H); LCMS m/z = 453.11 (M + 1, 100%)

3-Chloro-7-(2- ((3aS,4R,6aR)-2,2- dimethyl-4-(1H-pyrrolo[3,2-c]pyridin-1- yl)-3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.91(s, 1H), 8.20 (s, 1H), 8.09 (d, J = 6.2 Hz, 1H), 7.49 (d, J = 6.1 Hz,1H), 7.24 (s, 1H), 7.11 (d, J = 3.3 Hz, 1H), 7.07-7.01 (m, 1H), 6.98 (s,2H), 6.60 (d, J = 3.3 Hz, 1H), 5.58 (d, J = 1.8 Hz, 1H), 5.39 (s, 1H),5.18 (dd, J = 17.2, 6.7 Hz, 2H), 4.41 (t, J = 5.4 Hz, 1H), 3.84 (q, J =5.9 Hz, 1H), 3.11-2.91 (m, 2H), 2.68-2.58 (m, 2H); LCMS (m/z) = 439.23(M+, 100%).

3-chloro-7-(2- ((3aS,4R,6aR)-2,2- dimethyl-4-(7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR(400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.76 (s, 1H), 8.18 (s, 1H), 7.22 (s,1H), 7.11 (d, J = 3.6 Hz, 1H), 7.02 (dd, J = 11.1, 1.4 Hz, 1H), 6.96 (s,2H), 6.49 (d, J = 3.6 Hz, 1H), 5.65 (s, 1H), 5.47 (d, J = 1.9 Hz, 1H),5.03 (d, J = 6.4 Hz, 2H), 4.48 (t, J = 6.1 Hz, 1H), 4.06-4.02 (m, 1H),3.02-2.93 (m, 2H), 2.60-2.55 (m, 2H) ; LCMS m/z = 440.17 (M+, 60%)

N7-(((3aS,4R,6aR)-4-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H-cyclo penta[d][1,3]dioxol-6-yl)methyl)-N2-(4- methoxybenzyl) quinoline-2,7-diamine ¹H NMR (400 MHz,DMSO-d6) δ 8.04 (s, 1H), 7.60 (d, J = 8.6 Hz, 1H), 7.29 (d, J = 8.6 Hz,1H), 6.96-6.91 (m, 3H), 6.64 (dd, J = 8.7, 2.3 Hz, 1H), 6.51 (d, J = 3.5Hz, 1H), 6.48 (d, J = 2.2 Hz, 1H), 6.37 (d, J = 8.6 Hz, 1H), 6.20 (t, J= 5.6 Hz, 1H), 6.08 (s, 2H), 5.61 (q, J = 1.8 Hz, 1H), 5.55 (s, 1H),5.09-5.04 (m, 2H), 4.52 (t, J = 5.9 Hz, 1H), 4.11 (q, J = 5.8 Hz, 1H),3.90 (s, 2H); LCMS m/z = 404.16 (M+, 100%)

7-(((3aS,4R,6aR)-4-(4- Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3] dioxol-6-yl)methoxy)-3-chloro-5-fluoro-N-(4- methoxybenzyl)quinolin- 2-amine ¹H NMR (400 MHz,DMSO-d6) δ 8.58 (bs, 2H), 8.32 (s, 1H), 8.11 (s, 1H), 7.32 (d, J = 3.6Hz, 1H), 6.99 (bs, 2H), 6.89-6.83 (m, 2H), 6.81 (d, J = 2.3 Hz, 1H),5.82 (q, J = 1.8 Hz, 1H), 5.63 (d, J = 5.2 Hz, 1H), 5.27 (bs, 2H),4.93-4.80 (m, 2H), 4.56 (d, J = 5.7 Hz, 1H),4.21 (t, J = 5.6 Hz, 1H);LCMS m/z = 457.17 (M+, 70%)

7-(((3aR,6R,6aS)-6-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-6,6a-dihydro- 3aH- cyclopenta[d][1,3]dioxol- 4-yl)methoxy)-N-methylquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.12 (s, 1H), 8.00(d, J = 8.9 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.40 (d, J = 13.8 Hz,3H), 7.12 (d, J = 3.7 Hz, 1H), 7.03 (d, J = 8.9 Hz, 1H), 6.80 (d, J =9.0 Hz, 1H), 6.64 (d, J = 3.5 Hz, 1H), 5.82 (d, J = 2.0 Hz, 1H), 5.61(s, 1H), 5.30-5.08 (m, 2H), 4.86 (s, 2H), 4.60 (t, J = 5.6 Hz, 1H),4.28-4.04 (m, 2H) 3.05 (d, J = 4.6 Hz, 3H); LCMS m/z = 419.16 (M+, 100%)

7-(1-((3aS,4R,6aR)-4-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)ethoxy)-3-chloro-5- fluoro-N-(4- methoxybenzyl)quinolin- 2-amineDiastereomeric mixture was separated by chiral preparative HPLC. FirstDiastereomer (Compound- 20a): ¹H NMR (400 MHz, DMSO-d6) δ 8.12 (s, 1H),7.92 (s, 1H), 7.36 (d, J = 3.6 Hz, 1H), 7.16 (d, J = 3.5 Hz, 1H), 6.83(s, 2H), 6.65-6.35 (m, 3H), 5.96 (t, J = 9.7 Hz, 1H), 5.82-5.54 (m, 2H),5.07-4.91 (m, 2H), 4.61-4.36 (m, 2H), 4.18 (dd, J = 9.6, 4.8 Hz, 1H),1.65 (ddd, J = 26.6, 6.9, 2.5 Hz, 3H); LCMS m/z = 471.23 (M+, 90%)Second Diastereomer (Compound-20b): ¹H NMR (400 MHz, DMSO-d6) δ 8.08 (s,1H), 8.01 (s, 1H), 6.93 (s, 5H), 6.87-6.75 (m, 2H), 6.54 (d, J = 3.6 Hz,1H), 5.62 (d, J = 1.6 Hz, 1H), 5.53-5.49 (m, 1H), 5.26 (d, J = 5.9 Hz,1H), 5.23-5.13 (m, 2H), 4.55 (t, J = 5.7 Hz, 1H), 4.15-4.00 (m, 1H),1.57 (d, J = 6.5 Hz, 3H); LCMS m/z = 471.23 (M+, 80%)

3-chloro-7-(2- ((3aS,4R,6aR)-2,2- dimethyl-4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)quinolin-2- amine ¹H NMR (400 MHz,DMSO-d6) δ 8.62 (s, 1H), 8.17 (s, 1H), 7.61 (d, J = 8.3 Hz, 1H), 7.44(s, 1H), 7.37 (s, 1H), 7.17 (d, J = 8.2 Hz, 1H), 7.02 (d, J = 3.6 Hz,1H), 6.70 (s, 2H), 5.62 (s, 1H), 5.45 (s, 1H), 5.04 (s, 2H), 4.47 (d, J= 5.5 Hz, 1H), 4.14-3.91 (m, 1H), 3.06-2.87 (m, 2H) 2.58 (d, J = 32.3Hz, 5H); LCMS m/z = 436.23 (M+, 90%)

7-(2-((3aS,4R,6aR)-4-(4- Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol-6-yl)ethyl)-N-cyclo- butylquinolin-2-amine ¹H NMR (400 MHz,DMSO-d6) δ 8.15 (s, 1H), 8.05 (d, J = 9.1 Hz, 1H), 7.77-7.51 (m, 4H),7.24 (d, J = 8.1 Hz, 1H), 6.82 (dd, J = 17.2, 6.4 Hz, 2H), 6.57 (d, J =3.6 Hz, 1H), 5.53 (s, 1H), 5.45 (s, 1H), 5.03 (s, 2H), 4.55- 4.43 (m,2H), 4.01 (t, J = 5.2 Hz, 1H), 3.06-2.87 (m, 2H), 2.59- 2.54 (m, 2H),2.41 (d, J = 8.7 Hz, 2H), 2.01 (q, J = 9.8 Hz, 2H), 1.76 (q, J = 9.4 Hz,2H); LCMS m/z = 457.3 (M+, 90%)

Example-2:(1S,2R,5R)-3-(2-(2-Amino-3-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol(Compound-23)

The mixture of7-(2-((3aS,4R,6aR)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-fluoroquinolin-2-amine(0.060 g, 0.130 mmol) in TFA (1.004 ml, 13.03 mmol) was stirred at 25°C. for 6 h under N₂ atmosphere. The reaction mixture was basified withice cold solution of aq.sat.NaHCO₃ (20 ml) and extracted with ethylacetate (20 ml). Layers were separated, organic layer was washed withbrine (20 ml) and dried over anhydrous Na₂SO₄. The organic layer wasfiltered and concentrated in vacuo to give 0.12 g of crude compound.This residue was purified by combiflash (R_(f)200, Teledyne/Isco)instrument onto a Redisep® R_(f) column with gradient elution (0 to 10%)of methanol in dichloromethane to afford the title compound (25 mg,45.6% yield) as an off-white solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.05 (d,J=7.3 Hz, 1H), 7.79 (d, J=11.8 Hz, 1H), 7.59 (d, J=8.2 Hz, 1H), 7.37 (s,1H), 7.16 (d, J=8.3 Hz, 1H), 6.99 (s, 2H), 6.74 (s, 2H), 6.58 (d, J=3.5Hz, 1H), 6.40 (d, J=3.5 Hz, 1H), 5.50 (d, J=9.5 Hz, 1H), 5.42 (d, J=1.9Hz, 1H), 4.97 (dd, J=6.6, 3.1 Hz, 2H), 4.45 (t, J=6.0 Hz, 1H), 3.95 (q,J=5.5 Hz, 1H), 3.04-2.85 (m, 2H), 2.60-2.53 (m, 2H); LCMS m/z=420.92(M+, 100%).

Examples in table-14 were synthesized by following an analogous reactionprotocol as was used for the preparation of(1S,2R,5R)-3-(2-(2-amino-3-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-12-diolusing the appropriate starting materials (Instead of TFA, aq.TFA orFeCl₃.DCM could also be used at appropriate

TABLE 14 Structure & IUPAC name Intermediate used ¹H NMR & LCMS data

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-chloro-5- fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6)δ 8.17 (d, J = 0.8 Hz, 1H), 8.03 (s, 1H), 7.22 (s, 1H), 7.01 (dd, J =11.0, 1.4 Hz, 1H), 6.95 (s, 2H), 6.92 (s, 2H), 6.63 (d, J = 3.5 Hz, 1H),6.42 (d, J = 3.5 Hz, 1H), 5.50 (t, J = 3.2 Hz, 1H), 5.45 (t, J = 1.7 Hz,1H), 4.96 (dd, J = 6.3, 3.0 Hz, 2H), 4.45 (t, J = 5.8 Hz, 1H), 3.97 (q,J = 5.5 Hz, 1H), 3.03-2.87 (m, 2H), 2.56 (t, J = 7.0 Hz, 2H); LCMS m/z =454.98 (M+, 40%)

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-chloro-6- fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6)δ 8.17 (s, 1H), 8.03 (s, 1H), 7.53- 7.30 (m, 2H), 6.97 (s, 2H), 6.75-6.55 (m, 3H), 6.44 (d, J = 3.6 Hz, 1H), 5.57-5.31 (m, 2H), 4.98 (dd, J =6.4, 1.8 Hz, 2H), 4.45 (t, J = 6.0 Hz, 1H), 3.98 (q, J = 5.6 Hz, 1H),2.98 (q, J = 6.7 Hz, 2H), 2.59-2.52 (m, 2H); LCMS m/z = 455.10 (M+, 90%)

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-chloro-8- fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6)δ 8.24 (d, J = 1.6 Hz, 1H), 8.04 (s, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.17(dd, J = 8.3, 6.5 Hz, 1H), 7.00 (bs, 4H), 6.66 (d, J = 3.6 Hz, 1H), 6.44(d, J = 3.5 Hz, 1H), 5.51 (d, J = 4.5 Hz, 1H), 5.42 (d, J = 1.8 Hz, 1H),4.96 (dd, J = 6.6, 4.8 Hz, 2H), 4.44 (t, J = 5.9 Hz, 1H), 3.98 (q, J =5.6 Hz, 1H), 2.98 (d, J = 8.3 Hz, 2H), 2.49- 2.40 (m, 2H); LCMS m/z =455.05 (M+, 100%)

7-((3aS,4R,6aR)-6-(2- (2-amino-3,3-dimethyl- 3H-indol-6-yl)ethyl)-2,2-dimethyl-3a,6a- dihydro-4H- cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3- d]pyrimidin-4-amine ¹H NMR (400 MHz, DMSO-d6) δ8.04 (s, 1H), 7.02 (d, J = 7.3 Hz, 1H), 6.97-6.85 (m, 4H), 6.81 (d, J =1.4 Hz, 1H), 6.67 (dd, J = 7.4, 1.5 Hz, 1H), 6.63 (d, J = 3.5 Hz, 1H),6.46 (d, J = 3.5 Hz, 1H), 5.55-5.46 (m, 1H), 5.42 (t, J = 1.7 Hz, 1H),4.95 (s, 2H), 4.44 (d, J = 5.5 Hz, 1H), 3.93 (q, J = 4.8 Hz, 1H),2.87-2.62 (m, 2H), 2.49-2.41 (m, 2H), 1.30-1.17 (m, 6H); LCMS m/z =418.41 (M+, 100%)

6′-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol- 6-yl)ethyl)spiro[cyclobutane- 1,3′-indol]-2′-amine ¹H NMR (400 MHz,DMSO-d6) δ 8.04 (s, 1H), 7.39 (d, J = 7.3 Hz, 1H), 7.07 (s, 2H), 6.92(s, 2H), 6.77 (d, J = 1.4 Hz, 1H), 6.71 (dd, J = 7.5, 1.5 Hz, 1H), 6.62(d, J = 3.5 Hz, 1H), 6.45 (d, J = 3.5 Hz, 1H), 5.49 (d, J = 4.3 Hz, 1H),5.41 (d, J = 1.9 Hz, 1H), 4.93 (d, J = 5.9 Hz, 2H), 4.45 (d, J = 5.5 Hz,1H), 3.93 (q, J = 5.3 Hz, 1H), 2.87-2.64 (m, 2H), 2.62-2.49 (m, 4H),2.40-2.30 (m, 1H), 2.24-2.13 (m, 3H); LCMS m/z = 431.23 (M+, 50%)

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-3,5-dichloroquinolin-2- amine ¹H NMR (400 MHz, DMSO-d6) δ 8.20 (s, 1H), 8.03(s, 1H), 7.35 (d, J = 8.7 Hz, 2H), 7.14-6.88 (m, 4H), 6.62 (d, J = 3.5Hz, 1H), 6.43 (d, J = 3.6 Hz, 1H), 5.49 (s, 1H), 5.43 (s, 1H), 4.98 (dd,J = 11.2, 6.4 Hz, 2H), 4.46 (t, J = 5.9 Hz, 1H), 3.96 (q, J = 5.5 Hz,1H), 3.04-2.85 (m, 2H), 2.62-2.56 (m, 2H); LCMS m/z = 471.30 (M+, 50%)

7-(2-((3aS,4R,6aR)-4- (2-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-3-chloroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d₆) δ 8.69 (s, 1H), 8.37(s, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.42 (s, 1H), 7.26 (d, J = 8.3 Hz,1H), 6.95 (d, J = 3.9 Hz, 1H), 6.46 (d, J = 3.8 Hz, 1H), 5.42 (dd, J =10.5, 3.3 Hz, 2H), 5.30-4.81 (m, 2H), 4.47 (d, J = 5.5 Hz, 1H), 4.22-3.88 (m, 1H), 3.09-2.87 (m, 2H) 2.57 (d, J = 7.7 Hz, 2H); LCMS m/z =437.21 (M + 1, 70%)

3-chloro-5-fluoro-7-(2- ((3aS,4R,6aR)-4-(4- isopropyl-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)quinolin-2- amine ¹H NMR (400 MHz,DMSO-d6) δ 8.68 (s, 1H), 8.18 (s, 1H), 7.22 (s, 1H), 7.05 (d, J = 3.7Hz, 1H), 7.02 (dd, J = 11.0, 1.4 Hz, 1H), 6.96 (s, 2H), 6.57 (d, J = 3.6Hz, 1H), 5.63 (d, J = 4.5 Hz, 1H), 5.46 (d, J = 1.8 Hz, 1H), 5.01 (d, J= 6.5 Hz, 2H), 4.47 (t, J = 6.1 Hz, 1H), 4.10-3.98 (m, 1H), 3.40 (dt, J= 13.9, 6.9 Hz, 1H), 3.04-2.89 (m, 2H), 2.57 (d, J = 8.3 Hz, 2H), 1.32(d, J = 2.1 Hz, 3H), 1.30 (d, J = 2.1 Hz, 3H); LCMS m/z = 483.92 (M+,30%)

3-chloro-7-(2- ((3aS,4R,6aR)-2,2- dimethyl-4-(4-(1- methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-3a,6a- dihydro-4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR(400 MHz, DMSO-d6) δ 8.68 (s, 1H), 8.62 (s, 1H), 8.21 (d, J = 19.9 Hz,2H), 7.26-7.17 (m, 2H), 7.03 (dd, J = 11.0, 1.4 Hz, 2H), 6.98 (s, 1H),6.87 (d, J = 3.7 Hz, 1H), 5.66 (d, J = 4.6 Hz, 1H), 5.50 (t, J = 1.7 Hz,1H), 5.04 (d, J = 6.1 Hz, 2H), 4.48 (s, 1H), 4.08 (d, J = 5.4 Hz, 1H),3.97 (s, 3H), 3.06-2.88 (m, 2H), 2.60-2.55 (m, 2H); LCMS m/z = 520.32(M+, 100%)

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)propyl)-3-chloro- 5-fluoroquinolin-2- amine Diastereomeric mixturewas separated by chiral preparative HPLC. First Diastereomer(Compound-33a): ¹H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 8.03 (s, 1H),7.18 (s, 1H), 7.14-6.83 (m, 5H), 6.50 (d, J = 3.5 Hz, 1H), 6.42 (d, J =3.5 Hz, 1H), 5.51 (d, J = 5.1 Hz, 1H), 5.36 (d, J = 1.8 Hz, 1H), 5.00(d, J = 6.8 Hz, 1H), 4.89 (d, J = 6.2 Hz, 1H), 4.56 (t, J = 5.8 Hz, 1H),3.91 (d, J = 5.5 Hz, 1H), 3.08-2.94 (m, 1H), 2.79 (d, J = 9.3 Hz, 2H),1.09 (d, J = 6.7 Hz, 3H); LCMS m/z = 469.36 (M+, 30%) SecondDiastereomer (Compound-33b): ¹H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H),8.05 (s, 1H), 7.19 (s, 1H), 7.08- 6.86 (m, 5H), 6.78 (d, J = 3.5 Hz,1H), 6.50 (d, J = 3.5 Hz, 1H), 5.56-5.47 (m, 1H), 5.43 (t, J = 1.4 Hz,1H), 4.97 (t, J = 5.5 Hz, 2H), 4.51-4.42 (m, 1H), 3.98 (q, J = 6.1, 5.3Hz, 1H), 3.09-2.96 (m, 1H), 2.75 (s, 2H), 1.08 (d, J = 6.3 Hz, 3H); LCMSm/z = 469.36 (M+, 30%)

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol- 6-yl)propyl)-3-chloroquinolin-2-amine Diastereomeric mixture was separated by chiralpreparative HPLC. First Diastereomer (Compound-34a): ¹H NMR (400 MHz,DMSO-d6) δ 8.17 (s, 1H), 8.03 (s, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.33(d, J = 1.5 Hz, 1H), 7.13 (dd, J = 8.2, 1.6 Hz, 1H), 6.94 (s, 2H), 6.67(s, 2H), 6.47 (d, J = 3.5 Hz, 1H), 6.39 (d, J = 3.5 Hz, 1H), 5.56-5.46(m, 1H), 5.35 (d, J = 1.8 Hz, 1H), 4.98 (d, J = 6.7 Hz, 1H), 4.88 (d, J= 6.3 Hz, 1H), 4.57 (t, J = 5.9 Hz, 1H), 3.90 (q, J = 5.7 Hz, 1H),3.10-2.96 (m, 1H), 2.84- 2.73 (m, 2H), 1.13-1.09 (m, 3H); LCMS m/z =451.2 (M+, 100%) Second Diastereomer (Compound-34b): ¹H NMR (400 MHz,DMSO-d6) δ 8.17 (s, 1H), 8.05 (s, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.34(d, J = 1.6 Hz, 1H), 7.13 (dd, J = 8.2, 1.6 Hz, 1H), 6.94 (s, 2H), 6.77(d, J = 3.6 Hz, 1H), 6.67 (s, 2H), 6.49 (d, J = 3.5 Hz, 1H), 5.59- 5.49(m, 1H), 5.47-5.38 (m, 1H), 4.95 (t, J = 7.2 Hz, 2H), 4.47 (t, J = 6.0Hz, 1H), 3.98 (q, J = 5.5 Hz, 1H), 3.04 (dd, J = 12.0, 4.5 Hz, 1H),2.82-2.64 (m, 2H), 1.07 (d, J = 6.3 Hz, 3H); LCMS m/z = 452.98 (M + 1,80%)

3-chloro-7-(2- ((3aS,4R,6aR)-2,2- dimethyl-4-(4-methyl- 7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3a,6a- dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)propyl)-5- fluoroquinolin-2-amine Diastereomeric mixture wasseparated by chiral preparative HPLC. First Diastereomer (Compound-35a):¹H NMR (400 MHz, DMSO-d6) δ 8.63 (s, 1H), 8.18 (s, 1H), 7.27-7.12 (m,2H), 6.96 (s, 3H), 6.64 (d, J = 3.6 Hz, 1H), 5.64 (d, J = 4.9 Hz, 1H),5.46 (d, J = 2.0 Hz, 1H), 5.01 (dd, J = 6.5, 3.4 Hz, 2H), 4.46 (t, J =5.9 Hz, 1H), 4.03 (q, J = 5.7 Hz, 1H), 3.02 (q, J = 9.1 Hz, 1H), 2.86-2.68 (m, 2H), 2.64 (s, 3H), 1.09 (d, J = 7.0 Hz, 3H); LCMS m/z = 468.36(M+, 80%) Second Diastereomer (Compound-35b): ¹H NMR (400 MHz, DMSO-d6)δ 8.60 (s, 1H), 8.19 (s, 1H), 7.19 (s, 1H), 7.04-6.89 (m, 4H), 6.52 (d,J = 3.6 Hz, 1H), 5.63 (d, J = 5.0 Hz, 1H), 5.39 (d, J = 1.8 Hz, 1H),5.08-5.00 (m, 1H), 4.95 (d, J = 6.2 Hz, 1H), 4.58 (t, J = 5.9 Hz, 1H),3.98 (dt, J = 6.8, 5.4 Hz, 1H), 3.03 (q. J = 10.1 Hz, 1H), 2.81 (s, 2H),2.62 (s, 3H), 1.11 (d, J = 5.3 Hz, 3H); LCMS m/z = 468.36 (M+, 80%)

3-chloro-5-fluoro-7-(2- ((3aS,4R,6aR)-2,2,6a- trimethyl-4-(4-methyl-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-3a,6a- dihydro-4H-cyclopenta[d][1,3]dioxol- 6-yl)propyl)quinolin- 2-amine Diastereomericmixture was separated by chiral preparative HPLC. First Diastereomer(Compound 36a): ¹H NMR (400 MHz, DMSO-d6) δ 8.63 (s, 1H), 8.19 (s, 1H),7.22-7.12 (m, 2H), 7.03-6.90 (m, 3H), 6.66 (d, J = 3.7 Hz, 1H),5.64-5.54 (m, 2H), 5.05 (d, J = 7.1 Hz, 1H), 4.49 (s, 1H), 3.66 (t, J =6.5 Hz, 1H), 2.96 (dd, J = 13.2, 7.1 Hz, 1H), 2.85-2.68 (m, 2H), 2.65(s, 3H), 1.24 (s, 3H), 1.13 (d, J = 6.5 Hz, 3H): LCMS m/z = 482.2 (M+,40%) Second Diastereomer (Compound 36b): ¹H NMR (400 MHz, DMSO-d6) δ8.64 (s, 1H), 8.17 (s, 1H), 7.43 (d, J = 3.6 Hz, 1H), 7.21 (s, 1H), 7.00(dd, J = 11.1, 1.3 Hz, 1H), 6.95 (s, 2H), 6.69 (d, J = 3.6 Hz, 1H),5.68-5.61 (m, 1H), 5.46 (d, J = 1.4 Hz, 1H), 5.18 (d, J = 7.3 Hz, 1H),4.63 (s, 1H), 3.90 (t, J = 6.9 Hz, 1H), 3.23-3.16 (m, 1H), 2.73 (s, 2H),2.65 (s, 3H), 1.42 (s, 3H), 0.99 (d, J = 6.6 Hz, 3H); LCMS m/z = 482.2(M+, 40%).

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2,6a-trimethyl-3a,6a- dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-chloro-5- fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6)δ 8.17 (s, 1H), 8.12 (s, 1H), 7.34 (s, 2H), 7.22 (s, 1H), 7.07-6.92 (m,4H), 6.65-6.57 (m, 1H), 5.56- 5.41 (m, 2H), 5.15-4.99 (m, 1H), 4.62 (s,1H), 3.83 (d, J = 6.0 Hz, 1H), 2.99-2.86 (m, 2H), 2.46- 2.31 (m, 2H),1.27 (s, 3H); LCMS m/z = 469.30 (M+, 40%)

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2,6a-trimethyl-3a,6a- dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)propyl)-3-chloro- 5-fluoroquinolin-2- amine First Diastereomer: ¹HNMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 8.04 (s, 1H), 7.18 (s, 1H),7.01-6.90 (m, 5H), 6.70 (d, J = 3.6 Hz, 1H), 6.47 (d, J = 3.5 Hz, 1H),5.55 (d, J = 1.7 Hz, 1H), 5.47 (d, J = 5.9 Hz, 1H), 5.06 (d, J = 7.0 Hz,1H), 4.44 (s, 1H), 3.63 (dd, J = 7.0, 5.8 Hz, 1H), 2.97 (dd, J = 12.9,6.7 Hz, 1H), 2.82-2.68 (m, 2H), 1.24 (s, 3H), 1.11 (s, 3H); LCMS m/z =482.67 (M+, 80%)

3-chloro-5-fluoro-7-(2- ((3aS,4R,6aR)-2,2,6a- trimethyl-4-(4-methyl-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-3a,6a- dihydro-4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)quinolin-2- amine ¹H NMR (400 MHz,DMSO-d6) δ 8.63 (s, 1H), 8.17 (s, 1H), 7.38 (d, J = 3.7 Hz, 1H), 7.22(s, 1H), 7.02 (dd, J = 11.0, 1.5 Hz, 1H), 6.96 (s, 2H), 6.67 (d, J = 3.5Hz, 1H), 5.64-5.57 (m, 1H), 5.50- 5.45 (m, 1H), 5.07 (d, J = 7.3 Hz,1H), 4.65 (s, 1H), 3.89 (dd, J = 7.4, 6.1 Hz, 1H), 2.94 (t, J = 7.8 Hz,2H), 2.64 (s, 3H), 2.57- 2.53 (m, 2H), 1.28 (s, 3H); LCMS m/z = 468.36(M+, 60%)

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-6a-ethyl-2,2-dimethyl- 3a,6a-dihydro-4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-chloro-5- fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6)δ 8.16 (s, 1H), 8.05 (s, 1H), 7.22 (s, 1H), 7.07-6.89 (m, 6H), 6.56 (d,J = 3.6 Hz, 1H), 5.57-5.43 (m, 2H), 5.04 (d, J = 7.6 Hz, 1H), 4.56 (s,1H), 3.95 (t, J = 6.4 Hz, 1H), 2.94 (t, J = 8.0 Hz, 2H), 2.48-2.42 (m,2H), 1.69 (dq, J = 14.4, 7.2 Hz, 1H), 1.56 (dq, J = 14.4, 7.2 Hz, 1H),0.85 (t, J = 7.2 Hz, 3H); LCMS m/z = 482.67 (M+, 80%)

3-chloro-7-(2- ((3aS,4R,6aR)-4-(4- ethyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyl-3a,6a-dihydro- 4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR(400 MHz, DMSO-d6) δ 8.66 (s, 1H), 8.18 (s, 1H), 7.22 (s, 1H), 7.11-6.91(m, 4H), 6.56 (d, J = 3.6 Hz, 1H), 5.63 (s, 1H), 5.46 (d, J = 1.9 Hz,1H), 5.02 (dd, J = 6.5. 4.3 Hz, 2H), 4.47 (t, J = 6.0 Hz, 1H), 4.08-4.00(m, 1H), 2.96 (q, J = 7.7 Hz, 4H), 2.57 (d, J = 7.2 Hz, 2H), 1.31 (d, J= 7.6 Hz, 3H): LCMS m/z = 468.08 (M+, 100%)

3-Chloro-7-(2- ((3aS,4R,6aR)-4-(4- cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)-2,2-dimethyl- 3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol- 6-yl)ethyl)-5- fluoroquinolin-2-amine ¹H NMR(400 MHz, DMSO-d6) δ 8.63 (s, 1H), 8.27 (s, 1H), 7.30 (d, J = 36.5 Hz,3H), 7.18 (d, J = 3.7 Hz, 1H), 7.08 (d, J = 10.9 Hz, 1H), 6.76 (d, J =3.7 Hz, 1H), 5.62 (d, J = 3.7 Hz, 1H), 5.47 (d, J = 1.9 Hz, 1H), 4.47(d, J = 5.5 Hz, 1H), 4.06 (t, J = 5.2 Hz, 1H), 3.07-2.88 (m, 2H),2.62-2.54 (m, 3H) 1.27-1.14 (m, 4H); LCMS m/z = 479.86 (M+, 100%)

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)ethyl)-3-bromo-5- fluoroquinolin-2-amine ¹H NMR (400 MHz, DMSO-d6)δ 8.34 (s, 1H), 8.04 (s, 1H), 7.21 (s, 1H), 7.06-6.94 (m, 3H), 6.86 (s,2H), 6.65 (d, J = 3.5 Hz, 1H), 6.43 (d, J = 3.5 Hz, 1H), 5.49 (d, J =4.4 Hz, 1H), 5.45 (t, J = 1.7 Hz, 1H), 4.96 (dd, J = 6.5, 2.1 Hz, 2H),4.45 (t, J = 6.0 Hz, 1H), 3.97 (q, J = 5.5 Hz, 1H), 3.04-2.86 (m, J =7.4 Hz, 2H), 2.55 (d, J = 6.4 Hz, 2H); LCMS m/z = 499.30, 501.24 (M+,M + 2, 100%)

¹H NMR (400 MHz, DMSO-d6) δ 8.61 (s, 1H), 8.34 (s, 1H), 7.21 (s, 1H),7.06 (d, J = 3.6 Hz, 1H), 7.02-6.98 (m, 1H), 6.87 (s, 2H), 6.54 (d, J =3.6 Hz, 1H), 5.61 (t, J = 3.3 Hz, 1H), 5.46 (q, J = 1.6 Hz, 1H), 5.01(dd, J = 6.5, 5.2 Hz, 2H), 4.47 (t, J = 6.0 Hz, 1H), 4.08-3.99 (m, 1H),3.07-2.86 (m, 2H), 2.62 (s, 3H), 2.57 (t, J = 8.3 Hz, 2H); LCMS m/z =498.24, 500.24 (M+, M + 2, 100%).

7-(2-((3aS,4R,6aR)-4- (4-amino-7H- pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyl-3a,6a-dihydro- 4H- cyclopenta[d][1,3]dioxol-6-yl)propyl)-3-bromo- 5-fluoroquinolin-2- amine First Diastereomer(Compound 45a): ¹H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.03 (s, 1H),7.18 (s, 1H), 7.11-6.68 (m, 5H), 6.52 (d, J = 3.7 Hz, 1H), 6.41 (d, J =3.4 Hz, 1H), 5.51 (d, J = 4.8 Hz, 1H), 5.37 (s, 1H), 5.00 (d, J = 7.1Hz, 1H), 4.89 (d, J = 6.2 Hz, 1H), 4.56 (s, 1H), 3.91 (d, J = 6.2 Hz,1H), 3.01 (d, J = 7.4 Hz, 1H), 2.88-2.71 (m, 2H), 1.10 (d, J = 7.1, Hz,3H). LCMS m/z = 514.19 (M + 1, 100%) Second Diastereomer (Compound 45b):¹H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.04 (s, 1H), 7.18 (s, 1H),7.02-6.92 (m, 3H), 6.86 (s, 2H), 6.78 (d, J = 3.5 Hz, 1H), 6.50 (d, J =3.5 Hz, 1H), 5.52 (d, J = 4.8 Hz, 1H), 5.43 (s, 1H), 4.97 (dd, J = 6.5,3.6 Hz, 2H), 4.46 (t, J = 6.1 Hz, 1H), 3.98 (q, J = 5.6 Hz, 1H), 3.01(d, J = 9.0 Hz, 1H), 2.84-2.65 (m, 2H), 1.07 (d, J = 5.9 Hz, 3H). LCMSm/z = 514.19 (M + 1, 100%)

Example-3:(1S,2R,5R)-3-(2-(2-Amino-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol(Compound-46)

The mixture of(1S,2R,5R)-3-(2-(2-amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol(311 mg, 0.684 mmol) and palladium hydroxide (168 mg, 0.239 mmol) inethanol (40 ml) was stirred at 25° C. for 8 h under hydrogen atmosphere(60 psi). The resulting mixture was filtered through celite and filtratewas concentrated in vacuo to give 0.32 g of crude compound. Obtainedresidue was purified by combiflash (R_(f)200, Teledyne/Isco) instrumentonto a Redisep® R_(f) column with gradient elution (0 to 10%) ofmethanolic ammonia in dichloromethane to afford the title compound (7mg, 2.4% yield) as an off-white solid. ¹H NMR (400 MHz, DMSO-d6) δ 8.03(s, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.40 (t, J=9.3 Hz, 2H), 6.91 (s, 2H),6.75 (d, J=8.8 Hz, 1H), 6.65 (d, J=3.6 Hz, 1H), 6.43 (d, J=3.6 Hz, 1H),6.36 (s, 2H), 5.51 (s, 1H), 5.45 (s, 1H), 4.97 (d, J=6.3 Hz, 2H), 4.46(s, 1H), 3.97 (d, J=5.7 Hz, 1H), 3.05-2.88 (m, 2H), 2.48-2.26 (m, 2H).

LCMS m/z=420.98 (M+, 50%).

Example-4:(1S,2R,5R)-3-(2-(2-amino-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol(Compound-47)

The mixture of(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol(30 mg, 0.066 mmol), Pd—C (1.755 mg, 1.649 μmol) and ammonium formate(16.63 mg, 0.264 mmol) in MeOH (2 ml) was stirred at 78° C. for 8 h. Theresulting mixture was filtered through celite and filtrate wasconcentrated in vacuo to give 0.32 g of crude compound. Obtained residuewas purified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0 to 10%) of methanolicammonia in dichloromethane to afford the title compound (9 mg, 32.5%) asan off-white solid. ¹H NMR (400 MHz, DMSO-d6) Q 8.03 (s, 1H), 7.97 (d,J=9.0 Hz, 1H), 7.15 (s, 1H), 6.94-6.87 (m, 3H), 6.77 (d, J=9.0 Hz, 1H),6.64-6.59 (m, 3H), 6.41 (d, J=3.5 Hz, 1H), 5.49 (d, J=3.9 Hz, 1H), 5.44(t, J=1.7 Hz, 1H), 4.97 (d, J=5.5 Hz, 2H), 4.46 (s, 1H), 3.96 (q, J=5.3Hz, 1H), 3.00-2.86 (m, 2H), 2.54 (d, J=10.1 Hz, 2H); LCMS m/z=420.98(M+, 90%).

Example-5:(1R,2R3S,4R5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-48)

TFA (44.3 ml, 575 mmol) was added to7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)-yl)ethyl)-3-chloro-5-fluoroquinolin-2-amine (4.5 g, 8.84 mmol) at 0° C. The resulting mixture wasstirred at 25° C. for 16 h under N₂ atmosphere. The solvent was removedin vacuo at 30° C. The obtained residue was dissolved with ethyl acetate(100 ml) and basified with aq.sat. NaHCO₃. Layers were separated,organic layer was washed with brine (50 ml) and dried over anhydrousNa₂SO₄. The organic layer was filtered and concentrated in vacuo to give5.1 g of crude compound. This residue was purified by combiflash(R_(f)200, Teledyne/Isco) instrument onto a Redisep® R_(f) column withgradient elution (0 to 10%) of methanol in dichloromethane to afford thetitle compound (2.8 g, 67.5%) as a light Brown solid. ¹H NMR (400 MHz,DMSO-d6) δ 8.16 (s, 1H), 8.07 (s, 1H), 7.21 (s, 1H), 7.04 (d, J=3.6 Hz,1H), 7.03-6.99 (m, 1H), 6.99-6.90 (m, 4H), 6.58 (d, J=3.5 Hz, 1H), 5.12(d, J=3.8 Hz, 1H), 4.90 (s, 1H), 4.52 (d, J=4.1 Hz, 2H), 3.72 (s, 1H),2.96-2.80 (m, 2H), 2.14 (ddd, J=16.1, 11.3, 5.3 Hz, 1H), 1.84 (ddd,J=13.7, 11.2, 5.6 Hz, 1H), 1.24 (d, J=5.3 Hz, 2H), 0.57 (q, J=5.9 Hz,1H); LCMS m/z=469.23 (M+1, 50%).

Examples in table-15 were synthesized by following an analogous reactionprotocol as was used for the preparation of(1R,2R,3S,4R,5S)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2-(2-aminoquinolin-7-yl)ethyl)bicyclo[3.1.0]hexane-2,3-diolusing the appropriate starting materials.

TABLE 15 Structure & IUPAC name Intermediate used ¹H NMR & LCMS data

  Compound-49 (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimdiin-7-yl)-1-(2- (2-(methylamino)quinolin-7-yl)ethyl)bicyclo [3.1.0] hexane-2,3- diol 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethylhexahydrocyclo-propa [3,4]cyclopenta[1,2- d][1,3]dioxol-3b-yl)ethyl)-N-methylquinolin-2- amine ¹H NMR (400 MHz, DMSO- d6) δ 8.09 (s, 1H),7.91 (d, J = 9.0 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.52(s, 1H), 7.16(d, J = 8.2 Hz, 1H), 7.12-7.03 (m, 2H), 6.77 (d, J = 9.0 Hz, 1H), 6.61(d, J =3.5 Hz, 1H), 5.12 (d, J = 4.5 Hz, 1H), 4.91 (s, 1H), 4.53 (d, J=7.0 Hz, 2H), 3.74 (t, J = 5.0 Hz, 1H), 2.95 (d, J = 4.8 Hz, 3H),2.87-2.84 (m, 2H), 2.21-2.05 (m, 1H), 1.88 (ddd, J = 13.7, 11.5, 5.5 Hz,1H), 1.32- 1.19 (m, 2H), 0.61-0.58 (m, 1H); LCMS m/z = 431.06 (M + 1;60%).

  Compound-50 (1R,2R,3 S,4R,5 S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2- (2-(isopropylamino)quinolin-7-yl)ethyl)bicyclo [3.1.0]hexane-2,3- diol. 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo-propa [3,4]cyclopent[1,2- d][1,31dioxol-3b(3aH)- yl)ethyl)-N-isopropylquinolin-2- amine. ¹H NMR (400 MHz, DMSO- d6) δ 8.13 (s, 1H),7.99 (s, 1H), 7.70-7.53 (m, 2H), 7.27 (d, J = 38.6 Hz, 3H), 7.10 (d, J =3.6 Hz, 1H), 6.83 (d, J = 9.0 Hz, 1H), 6.66 (d, J = 3.5 Hz, 1H), 5.14(d, J = 4.4 Hz, 1H), 4.91 (d, J = 1.3 Hz, 1H), 4.54 (d, J = 3.2 Hz, 2H),4.31-4.18 (m, 1H) 3.75 (s, 1H), 3.03-2.80 (m, 2H), 2.14 (ddd, J = 17.0,11.9, 6.1 Hz, 1H), 1.94-1.79 (m, 1H), 1.27-1.23 (m, 8H), 0.64-0.54 (m,1H); LCMS m/z = 459.3 (M + 1; 100%)

  Compound-51 (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2- (2-(cyclobutylamino)quinolin-7-yl)ethyl)bicyclo [3.1.0]hexane-2,3- diol. 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo-propa [3,4]cyclopenta[1,2- d][1,31dioxol-3b(3aH)-yl)ethyl)-N-cyclobutyl- quinolin-2-amine. ¹H NMR (400 MHz, DMSO- d6) δ8.13 (s, 1H), 7.96 (d, J = 9.2 Hz, 1H), 7.62 (d, J = 8.1 Hz, 1H), 7.52(s, 1H), 7.29 (s, 1H), 7.19 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 3.6 Hz,1H), 6.77 (d, J = 9.1 Hz, 1H), 6.65 (d, J = 3.5 Hz, 1H), 5.13 (d, J =4.5 Hz, 1H), 4.91 (d, J = 1.3 Hz, 1H), 4.57- 4.45 (m, 3H), 3.75 (s, 1H),3.17 (s, 1H), 2.95-2.85 (m, 2H), 2.45-2.33 (m, 2H), 2.13 (ddd, J = 13.4,11.3, 5.2 Hz, 1H),2.06- 1.81 (m, 2H), 1.74 (ddd, J = 15.3, 10.1, 7.1 Hz,2H), 1.33- 1.21 (m, 2H), 0.64-0.55 (m, 1H); LCMS m/z = 471.3 (M + 1;100%).

  Compound-52 (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2- (2-((cyclopropylmethyl)amino)quinolin-7-yl) ethyl)bicyclo[3.1.0]hexane-2,3-diol 7-(2-((3aR,3bR,4aS,5R,5aS)-5- (4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclo- propa [3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)- yl)ethyl)-N-(cyclopropyl-methyl)quinolin-2-amine. ¹H NMR (400 MHz, DMSO- d6) δ 8.10 (s, 1H), 7.89(d, J = 9.0 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.46 (s, 1H), 7.18-7.04(m, 4H), 6.81 (d, J = 9.0 Hz, 1H), 6.61 (d, J = 3.5 Hz, 1H), 5.12 (d, J= 4.4 Hz, 1H), 4.91 (d, J = 1.2 Hz, 1H), 4.53 (d, J = 5.6 Hz, 2H), 3.74(t, J = 4.8 Hz, 1H), 3.31-3.28 (m, 1H), 2.94- 2.83 (m, 2H), 2.12 (ddd, J= 13.7, 11.5, 5.2 Hz, 1H), 1.88 (ddd, J = 13.7, 11.5, 5.4 Hz, 1H),1.28-1.23 (m, 3H), 1.19- 1.08 (m, 1H), 0.59 (q, J = 5.9 Hz, 1H), 0.53 -0.45 (m, 2H), 0.33-0.22 (m,2H); LCMS m/z = 471.05(M + 1; 90%).

  Compound-53 (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2- (2-amino-8-fluoroquinolin-7-yl)ethyl)bicyclo [3.1.0]hexane-2,3- diol. 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo-propa [3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)ethyl)-8-fluoroquinolin- 2-amine. ¹H NMR (400 MHz, DMSO- d6) δ 8.10(s, 1H), 7.90 (dd, J = 9.0, 1.6Hz, 1H), 7.38 (d, J = 8.2 Hz, 1H),7.30-7.00 (m, 4H), 6.77 (d, J = 9.1 Hz, 3H), 6.62 (d, J = 3.6 Hz, 1H),5.15 (d, J = 4.5 Hz, 1H), 4.91 (s, 1H), 4.53 (d, J = 3.0 Hz, 2H), 3.75(s, 1H), 2.97 (td, J = 12.6, 5.1 Hz, 1H), 2.84 (td, J = 12.6, 5.3 Hz,1H), 2.19-2.01 (m, 1H), 1.82 (td, J= 12.7, 5.2 Hz, 1H), 1.28 (d, J = 3.5Hz, 2H), 0.63-0.54 (m, 1H); LCMS m/z = 435.04 (M + 1; 40 %).

  Compound-54 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-methylquinolin-7-yl)ethyl)-4-(4- amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl) bicyclo[3.1.0]hexane-2,3-diol. 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,31dioxol-3b(3aH)- yl)ethyl)-3-methylquinolin-2-amine. ¹H NMR (400 MHz, DMSO- d6) δ 8.07 (s, 1H), 7.71(s, 1H), 7.51 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 1.6 Hz, 1H), 7.08 (dd, J= 8.2, 1.7 Hz, 1H), 7.03 (d, J = 3.6 Hz, 1H), 6.98 (s, 2H), 6.58 (d, J =3.5 Hz, 1H),6.36 (s, 2H), 5.12 (d, J = 4.5 Hz, 1H), 4.90 (d, J = 1.2 Hz,1H), 4.59-4.46 (m, 2H), 3.72 (t, J = 5.2 Hz,1H), 2.92-2.83 (m, 2H), 2.20(d, J = 1.1 Hz, 3H), 2.10 (ddd, J = 12.7, 11.0, 5.2 Hz, 1H), 1.88 (ddd,J = 13.8, 11.5, 5.5 Hz, 1H), 1.23 (d, J = 3.5 Hz, 2H), 0.58 (q, J = 5.5Hz, 1H); LCMS m/z = 431.08 (M + 1; 100%).

  Compound-55 (1R,2R,3S,4R,5S)-1-(2-(2-Amino- 3-isopropylquinolin-7-yl)ethyl)-4- (4-amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol. 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)- yl)ethyl)-3-isopropylquinolin-2-amine ¹H NMR (400 MHz, DMSO- d6) δ 8.09 (d, J = 6.3Hz, 2H), 7.74 (d, J = 8.2 Hz, 3H), 7.45 (s, 1H), 7.30(dd, J = 8.1, 1.5Hz, 1H), 7.07 (dd, J = 9.1, 3.6 Hz, 3H), 6.61 (d, J = 3.5 Hz, 1H), 5.16(d, J = 4.5 Hz,1H), 4.90 (d, J = 1.2 Hz, 1H), 4.53 (d, J = 7.5 Hz, 2H),3.74 (t, J = 5.1 Hz, 1H), 3.10 (p, J = 6.7 Hz, 1H), 3.01-2.83 (m, 2H),2.14 (ddd, J = 15.8, 12.1, 6.4 Hz, 1H), 1.85 (ddd, J = 13.6, 11.1, 5.9Hz, 1H), 1.26 (d, J = 6.6 Hz, 8H), 0.56 (q, J =6.0 Hz, 1H); LCMS m/z =459.3 (M+; 40%).

  Compound-56 (1R,2R,3 S,4R,5S)-1-(2-(2-Amino- 3-(1,1-difluoroethyl)quinolin-7- yl)ethyl)-4-(4-amino-7H-pyrrolo [2,3-d] pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol. 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo-propa [3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)ethyl)-3-(1,1-difluoro- ethyl)quinolin-2-amine. ¹H NMR (400 MHz,DMSO- d6) δ 8.15 (s, 1H), 8.09 (s, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.38(s, 1H), 7.21-7.15 (m, 1H), 7.10- 7.00 (m, 3H), 6.61 (d, J = 3.6 Hz,1H), 6.25 (s, 2H), 5.11 (d, J= 4.5 Hz, 1H), 4.91 (s, 1H), 4.53 (d, J =7.5 Hz, 2H), 3.74 (t, J = 5.2 Hz, 1H), 2.83-2.91 (m, 2H), 2.18-1.98 (m,4H), 1.88 (td, J = 12.4, 5.5 Hz, 1H), 1.28- 1.25 (m, 2H), 0.58 (q, J =5.9 Hz, 1H); LCMS m/z = 481.2 (M + 1; 90%).

  Compound-57 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-cyclopropylquinolin-7-yl)ethyl)- 4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl) bicyclo[3.1.0]hexane-2,3-diol. 7-(2-((3aR,3bR,4aS,5R,5aS)-5- (4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclo propa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)ethyl)-3-cyclopropyl- quinolin-2-amine. ¹H NMR (400 MHz, DMSO- d6) δ8.09 (s, 1H), 7.91 (s, 1H), 7.80 (s, 2H), 7.67 (d, J = 8.2 Hz, 1H), 7.44(s, 1H), 7.27 (dd, J = 8.2, 1.5 Hz, 1H), 7.11 (s, 2H), 7.06 (d, J = 3.5Hz, 1H), 6.61 (d, J = 3.5 Hz, 1H), 5.17 (d, J = 4.5 Hz, 1H), 4.90 (d, J= 1.2 Hz, 1H), 4.53 (d, J = 4.3 Hz, 2H), 3.73 (s, 1H), 2.95-2.87 (m,2H), 2.12 (ddd, J = 13.8, 11.0, 5.4 Hz, 1H), 1.90-1.74 (m, 2H), 1.23 (d,J = 3.4 Hz, 2H), 1.08-0.96 (m, 2H), 0.78-0.68 (m, 2H), 0.55 (q, J = 5.8Hz, 1H); LCMS m/z = 457.13 (M+; 50%).

  Compound-58 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-methoxyquinolin-7-yl)ethyl)-4- (4-amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol. 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)- yl)ethyl)-3-methoxyquinolin-2-amine. ¹H NMR (400 MHz, DMSO- d6) δ 8.08 (s, 1H), 7.54(d, J = 8.1 Hz, 1H), 7.40-7.31 (m, 2H), 7.15-7.05 (m, 3H), 7.04 (d, J =3.5 Hz, 1H), 6.67 (d, J = 18.5 Hz, 2H), 6.60 (d, J = 3.5 Hz, 1H), 5.12(d, J = 4.5 Hz, 1H), 4.90 (d, J = 1.3 Hz, 1H), 4.52 (d, J = 5.8 Hz, 2H),3.91 (s, 3H), 3.79-3.66 (m, 1H), 2.90- 2.80 (m, 2H), 2.09 (ddd, J =13.7, 11.2, 5.4 Hz, 1H), 1.88 (ddd, J = 13.8, 11.5, 5.7 Hz, 1H), 1.24(d, J = 5.2 Hz, 2H), 0.58 (q, J = 5.8 Hz, 1H). ); LCMS m/z = 447.01 (M +1; 90%).

  Compound-59 2-amino-7-(2-((1R,2R,3S,4R,5S)-4- (4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,3- dihydroxybicyclo [3.1.0]hexan-1-yl)ethyl)quinoline-3-carbonitrile. 2-amino-7-(2-((3aR,3bR,4aS,5R,5aS)-5- (4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyltetra hydrocyclopropa[3,4]cyclo- penta[1,2-d][1,31dioxol-3b(3aH)-yl)ethyl) quinoline-3-carbonitrile. ¹H NMR (400 MHz, DMSO- d6) δ8.62 (s, 1H), 8.06 (d, J = 2.3 Hz, 1H), 7.66 (d, J = 8.3 Hz, 1H),7.37(s, 1H), 7.22 (dd, J = 8.3, 1.6 Hz, 1H), 7.03 (d, J = 3.6 Hz, 1H),6.97 (s, 2H), 6.89 (s, 2H), 6.58 (d, J = 3.5 Hz, 1H), 5.11 (d, J = 4.5Hz, 1H), 4.90 (s, 1H), 4.57-4.48 (m, 2H), 3.73 (t, J = 5.3 Hz, 1H),3.0-2.81 (m, 2H), 2.21-2.04 (m, 1H) 1.93-1.81 (m, 1H), 1.26-1.23 (m,2H), 0.57 (q, J = 5.9 Hz, 1H); LCMS m/z = 442.23 (M + 1; 80%).

  Compound-60 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-fluoroquinolin-7-yl)ethyl)-4-(4- amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol. 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2- d][1,31dioxol-3b(3aH)-yl)ethyl)-3-fluoroquinolin- 2-amine. ¹H NMR (400 MHz, DMSO- d6) δ 8.15(s, 1H), 7.78 (d, J = 11.8 Hz, 1H), 7.58 (d, J = 8.2 Hz, 1H), 7.49 (s,2H), 7.37 (d, J= 1.6 Hz, 1H), 7.15 (dd, J = 8.2, 1.6 Hz, 1H), 7.11 (d, J= 3.6 Hz, 1H), 6.77 (s, 2H), 6.67 (d, J = 3.6 Hz, 1H), 5.14 (d, J = 4.3Hz, 1H), 4.90 (d, J = 1.3 Hz, 1H), 4.54 (d, J = 8.9 Hz, 2H), 3.74 (d, J= 5.5 Hz, 1H), 2.92-2.82 (m, 2H), 2.10 (ddd, J = 13.8, 11.2, 5.4 Hz,1H), 1.87 (ddd, J = 13.8, 11.6, 5.6 Hz, 1H), 1.27- 1.23 (m, 2H),0.63-0.55 (m, 1H). ); LCMS m/z = 435.3 (M+; 80%).

  Compound-61 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloroquinolin-7-yl)ethyl)-4-(4- amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol. 7-(2- ((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,31dioxol-3b(3aH)- yl)ethyl)-3-chloroquinolin-2-amine. ¹H NMR (400 MHz, DMSO- d6) δ 8.15 (s, 1H), 8.07(s, 1H), 7.58 (d, J = 8.2 Hz, 1H), 7.36 (s, 1H), 7.15(dd, J = 8.2, 1.6Hz, 1H), 7.08-6.89 (m, 3H), 6.66 (s, 2H), 6.58 (d, J = 3.5 Hz, 1H), 5.11(d, J = 4.5 Hz,1H), 4.90 (s, 1H), 4.55-4.50 (m, 2H), 3.73 (t, J = 5.3Hz, 1H), 2.96-2.80 (m, 2H), 2.11 (ddd, J = 13.7, 11.3, 5.3 Hz, 1H), 1.87(ddd, J = 13.9, 11.6, 5.6 Hz, 1H), 1.26- 1.23 (m, 2H), 0.58 (q, J = 5.9Hz, 1H); LCMS m/z = 451.3 (M + 1; 80%).

  Compound-62 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-6-fluoroquinolin-7- yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl) bicyclo[3.1.0]hexane-2,3-diol. 7-(2-((3aR,3bR,4aS,5R,5aS)-5- (4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)- yl)ethyl)-3-chloro-6- fluoroquinolin-2-amine. ¹HNMR (400 MHz, DMSO- d6) δ 8.15 (d, J = 6.2 Hz, 2H), 7.56-7.35 (m, 4H),7.13 (d, J = 3.6 Hz,1H), 6.68 (d, J = 3.1 Hz, 3H), 5.16 (s, 1H), 4.91(s, 1H), 4.53 (d, J = 7.2 Hz, 2H), 3.75 (s, 1H), 2.98 (t, J = 12.0 Hz,1H), 2.91-2.78 (m, 1H), 2.13 (q, J = 8.2, 4.7 Hz, 1H), 1.89-1.76(m, 1H),1.25 (d, J = 11.4 Hz, 2H), 0.59 (q, J = 6.0 Hz, 1H); LCMS m/z = 451.3(M + 1; 80%).

  Compound-63 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-8-fluoroquinolin-7- yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimdiin-7- yl)bicyclo[3.1.0]hexane-2,3-diol. 7-(2-((3aR,3bR,4aS,5R,5aS)-5- (4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)- yl)ethyl)-3-chloro-8- fluoroquinolin-2-amine. ¹HNMR (400 MHz, DMSO- d6) δ 8.23 (s, 1H), 8.07 (s, 1H), 7.42 (d, J = 8.3Hz, 1H), 7.17 (t, J = 7.4 Hz, 1H), 7.04 (d, J = 3.6 Hz, 1H), 7.01-6.92(m, 4H), 6.58 (d, J = 3.5 Hz, 1H), 5.16 (d, J = 4.6 Hz, 1H), 4.90 (s,1H), 4.59-4.44 (m, 2H), 3.73 (t, J = 5.4 Hz, 1H), 3.09-2.92 (m, 1H),2.92-2.77 (m, 1H) 2.13 (t, J = 7.2 Hz, 1H), 1.87-1.74 (m, 1H), 1.27 (t,J = 6.5 Hz, 2H), 0.58 (d, J = 5.6 Hz, 1H); LCMS m/z = 468.68 (M+; 80%).

  Compound-64 (1R,2R,3S,4R,5S)-1-(2-(2-amino-3-bromo-6-fluoroquinolin-7- yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7- yl)bicyclo[3.1.0]hexane-2,3-diol. 7-(2-((3aR,3bR,4aS,5R,5aS)-5- (4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)- yl)ethyl)-3-bromo-6- fluoroquinolin-2-amine. ¹HNMR (400 MHz, DMSO- d6) δ 8.35 (s, 1H), 8.24 (s, 1H), 7.96 (d, J = 30.9Hz, 2H), 7.45 (t, J = 8.4 Hz, 1H), 7.24 (d, J = 3.6 Hz, 1H), 6.80 (d, J= 3.5 Hz, 1H), 6.60 (s, 1H), 5.17 (s, 1H), 4.91 (d, J = 4.0 Hz,1H), 4.53(s, 1H), 4.40 (d, J = 6.8 Hz, 1H), 3.78 (d, J = 6.4 Hz, 1H), 3.04- 2.80(m, 2H), 2.15 (s, 1H), 1.82 (s, 1H), 1.30-1.27 (m, 2H), 0.60-0.55 (m,1H); LCMS m/z = 514.19 (M + 1; 80%).

  Compound-65 (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2- (3-methylimidazo[1,2-a]pyridin-7-yl)ethyl) bicyclo [3.1.0]hexane-2,3- diol. 7-((3aR,3bR,4aS,5R,5aS)-2,2-Dimethyl-3b-(2-(3- methylimidazo[1,2- a]pyridin-7-yl)ethyl)hexahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin- 4-amine. ¹H NMR (400MHz, DMSO- d6) δ 8.16 (d, J = 6.9 Hz, 1H), 8.07 (s, 1H), 7.36 (s, 1H),7.28 (s, 1H), 7.08-6.85 (m, 4H), 6.58 (d, J = 3.4 Hz, 1H), 5.12 (d, J =4.5 Hz, 1H), 4.90 (s, 1H), 4.52 (s, 2H), 3.72 (s, 1H), 3.29 (s, 1H),2.95-2.75 (m, 2H), 2.61- 2.53 (m, 1H), 2.44 (s, 3H), 2.21-2.03 (m, 1H),1.97-1.74 (m, 1H), 0.61-0.47(m, 1H); LCMS m/z = 405.16 (M + 1; 100%).

  Compound-66 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3,3-dimethyl-3H-indol-6-yl)ethyl)- 4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl) bicyclo[3.1.0]hexane-2,3-diol.7-((3aR,3bR,4aS,5R,5aS)- 3b-(2-(2-Amino-3,3- dimethyl-3H-indol-6-yl)ethyl)-2,2- dimethylhexahydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-7H- pyrrolo[2,3-d]pyrimidin- 4-amine. ¹H NMR (400MHz, DMSO- d6) δ 8.06 (s, 1H), 7.09 (d, J = 7.4 Hz, 1H), 7.01 (d, J =3.6 Hz, 1H), 6.98 (s, 2H), 6.87 (d, J = 1.4 Hz, 1H), 6.79-6.74 (m, 1H),6.58 (d, J = 3.5 Hz, 1H), 5.11 (s, 1H), 4.90 (d, J = 1.2 Hz, 1H), 4.49(s, 2H), 3.71 (s, 1H), 2.82-2.59 (m, 2H), 2.09-1.96 (m, 1H), 1.81 (td, J= 12.7, 5.3 Hz, 1H), 1.30 (s, 6H), 1.26- 1.19 (m, 2H),0.63-0.51 (m, 1H);LCMS m/z = 433.40 (M + 1; 80%).

  Compound-67 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7- yl)ethyl)-4-(4-amino-6-methyl-7H-pyrrolo[2,3-d] pyrimidin-7- yl)bicyclo[3.1.0]hexane-2,3-diol. 7-(2-((3aR,3bR,4aS,5R,5aS)-5- (4-Amino-6-methyl-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetra hydrocyclopropa[3,4]cyclo-penta[1,2-d][1,31dioxol- 3b(3aH)-yl)ethyl)-3- chloro-5-fluoroquinolin-2-amine. ¹H NMR (400 MHz, DMSO- d6) δ 8.15 (s, 1H), 8.03 (s, 1H), 7.18 (s,1H), 7.06-6.87 (m, 5H), 6.36-6.29 (m, 1H), 4.93 (d, J = 5.4 Hz, 1H),4.74 (t, J = 6.7 Hz, 1H), 4.51 (d, J = 6.6 Hz, 1H), 4.41 (d, J = 3.4 Hz,1H), 4.28 (s, 1H), 2.95 (td, J = 12.6, 11.3, 4.9 Hz, 1H), 2.82 (td, J =12.8, 12.1, 5.7 Hz, 1H), 2.38 (s, 3H), 2.14-1.98 (m, 1H), 1.79 (ddd, J =13.6, 11.3, 5.8 Hz, 1H), 0.99-0.79 (m, 2H), 0.58 (dd, J = 8.4, 4.7 Hz,1H); LCMS m/z = 485.05 (M + 2; 40%).

  Compound-68 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-6-fluoroquinolin-7- yl)ethyl)-4-(4-amino-6-methyl-7H-pyrrolo[2,3-d] pyrimidin-7- yl)bicyclo[3.1.0]hexane-2,3-diol. 7-(2-((3aR,3bR,4aS,5R,5aS)-5- (4-Amino-6-methyl-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetra- hydrocyclo- propa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)- yl)ethyl)-3-chloro-6- fluoroquinolin-2-amine. ¹HNMR (400 MHz, DMSO- d6) δ 8.15 (s, 1H), 8.01 (s, 1H), 7.46-7.39 (m, 2H),6.94 (s, 2H), 6.67 (s, 2H), 6.32 (d, J = 1.2 Hz, 1H), 4.98-4.91 (m,1H),4.76 (t, J = 6.7 Hz, 1H), 4.53 (d, J = 6.6 Hz, 1H), 4.42 (d, J = 3.4Hz, 1H), 4.28 (s, 1H), 3.08-2.94 (m, 1H), 2.84 (td, J = 13.3, 12.7, 5.3Hz, 1H), 2.43- 2.37 (m, 3H), 2.04 (dq, J = 19.8, 7.7, 6.3 Hz, 1H), 1.86-1.72 (m, 1H), 1.32-1.26 (m, 2H), 0.59 (dd, J = 8.3, 4.7 Hz, 1H); LCMSm/z = 482.30 (M; 80%).

  Compound-69 (1R,2R,3S,4R,5S)-1-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)- 4-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl) bicyclo[3.1.0]hexane-2,3-diol. 3-Chloro-7-(2-((3aR,3bR,4aS,5R,5aS)- 2,2-dimethyl-5-(4-methyl- 7H-pyrrolo [2,3-d]pyrimidin-7- yl)tetrahydrocyclo propa[3,4]cyclopenta[1,2-d][1,31dioxol-3b(3aH)- yl)ethyl)-5-fluoroquinolin- 2-amine. A mixture oftwo compound was separated by reverse phase HPLC to afford compound Xand compound Y as shown below. ¹H NMR (400 MHz, DMSO-d6) δ 8.66 (s, 1H),8.16 (s, 1H), 7.43 (d, J = 3.7 Hz, 1H), 7.21 (s, 1H), 7.00 (dd, J =11.1, 1.4 Hz, 1H), 6.93(s, 2H), 6.70 (d, J = 3.6 Hz, 1H), 5.16 (s, 1H),4.99 (d, J = 1.4 Hz, 1H), 4.56 (d, J = 6.5 Hz, 2H), 3.80 (d, J = 5.8 Hz,1H), 2.97-2.80 (m, 2H), 2.65 (s, 3H), 2.22-2.09 (m, 1H), 1.91-1.81 (m,1H), 1.31-1.25 (m, 2H), 0.60 (q, J = 5.8 Hz, 1H) ); LCMS m/z = 468.2(M + 1; 80%).

  Compound-70 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7- yl)ethyl)-4-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo [3.1.0]hexane-2,3-diol. 3-Chloro-7-(2-((3aR,3bR,4aS,5R,5aS)- 2,2-dimethyl-5-(7H- pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrocyclo propa- [3,4]cyclopenta[1,2- d][1,3]dioxol-3b(3aH)-yl)ethyl)-5-fluoroquinolin- 2-amine. ¹H NMR (400 MHz, DMSO- d6) δ 9.02(s, 1H), 8.81 (s, 1H), 8.16 (s, 1H), 7.51 (d, J = 3.7 Hz, 1H), 7.22 (s,1H), 7.03-6.98 (m, 1H), 6.92 (bs, 2H), 6.67 (d, J = 3.6 Hz, 1H), 5.02(d, J = 1.5 Hz, 1H), 4.56 (d, J = 6.7 Hz, 1H), 3.81 (d, J = 6.4 Hz, 1H),2.87 (ddd,J = 19.0, 14.0, 8.5 Hz, 2H), 2.20-2.10 (m, 1H), 1.88 (d, J =10.5 Hz, 1H), 1.32- 1.26 (m, 2H), 0.64-0.58 (m, 1H); LCMS m/z = 454.11(M + 1; 40%).

  Compound-71 (1R,2R,3 S,4R,5 S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2- (2′-aminospirocyclobutane-1,3′-indol]-6′-yl) ethyl)bicyclo[3.1.0]hexane-2,3- diol. 6′-(2-((3aR,3bR,4aS,5R,5aS)-5- (4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclo- propa [3,4]cyclopenta[1,2-d][1,3]dioxol-3b(3aH)- yl)ethyl)spiro[cyclobutane- 1,3′-indol]-2′-amine.¹H NMR (400 MHz, DMSO- d6) δ 8.07 (s, 1H), 7.68 (d, J = 7.7 Hz, 1H),7.22-7.07 (m, 4H), 7.07-6.96 (m, 3H) 6.59 (d, J = 3.5 Hz, 1H), 5.14 (d,J = 4.6 Hz, 1H), 4.89 (s, 1H), 4.51 (d, J = 7.2 Hz, 1H), 3.74 (t, J =5.4 Hz, 1H), 2.79 (dd, J = 24.0, 14.1 Hz, 3H), 2.35 (d, J = 12.3 Hz,2H), 2.20 (d, J = 9.9 Hz, 1H), 2.04 (d, J = 17.8 Hz, 1H), 1.87-1.74 (m,1H), 1.26-1.18 (m, 5H), 0.60-0.50 (m, 1H); LCMS m/z = 445.03 (M + 1;90%).

  Compound-72 (1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromo-5-fluoroquinolin-7- yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7- yl)bicyclo[3.1.0]hexane-2,3-diol

¹H NMR (400 MHz, DMSO- d6) δ 8.33 (s, 1H), 8.08 (s, 1H), 7.20 (s, 2H),7.17-6.96 (m, 3H), 6.84 (s, 2H), 6.60 (d, J = 3.5 Hz, 1H), 5.11 (d, J =4.5 Hz, 1H), 4.90 (d, J = 1.2 Hz, 1H), 4.52 (d, J = 2.7 Hz, 2H), 3.72(s, 1H), 3.00-2.74 (m, 2H), 2.14 (s, 1H), 1.90-1.76 (m, 1H), 1.42-1.28(m, 1H), 0.91-0.75 (m, 1H), 0.57 (q, J = 5.9 Hz, 1H); LCMS m/z = 514.19,516.19 (M+, M + 2, 100%).

Example-6:(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol (Compound-73)

7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-3b-yl)ethyl)-3-bromo-N-(4-methoxybenzyl)quinolin-2-amine (2.6 g, 3.97 mmol) in TFA (55.0 ml, 714 mmol)was stirred at 50° C. for 1 h under N₂ atmosphere. The resulting mixturewas concentrated in vacuo and obtained residue was dissolved in MeOH (50ml). K₂CO₃ (0.982 g, 7.10 mmol) was added and stirred the reactionmixture at 60° C. for 1 h. The reaction mixture was filtered, andfiltrate was concentrated under reduced pressure to get 2.7 g of crudecompound. This residue was purified by combiflash (R_(f)200,Teledyne/Isco) instrument onto a Redisep® R_(f) column with gradientelution (0 to 9%) of methanol in dichloromethane to afford the titlecompound (1.35 g, 77%) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ8.34 (s, 1H), 8.12 (s, 1H), 7.58 (d, J=8.3 Hz, 1H), 7.36 (d, J=1.6 Hz,1H), 7.26 (s, 2H), 7.15 (dd, J=8.2, 1.7 Hz, 1H), 7.09 (d, J=3.5 Hz, 1H),6.64 (d, J=3.5 Hz, 1H), 6.60 (s, 2H), 5.13 (d, J=4.6 Hz, 1H), 4.97-4.83(m, 1H), 4.53 (d, J=3.9 Hz, 2H), 3.74 (s, 1H), 2.94-2.81 (m, 2H), 2.11(dt, J=11.2, 6.5 Hz, 1H), 1.87 (ddd, J=13.9, 11.5, 5.6 Hz, 1H),1.33-1.12 (m, 2H); 0.60-0.57 (m, 1H). LCMS m/z=494.99, 496.99 (M+, M+2;100%).

Examples in table-16 were synthesized by following an analogous reactionprotocol as was used for the preparation of(1R,2R,3S,4R,5S)-1-(2-(2-amino-3-bromoquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol using theappropriate starting materials.

TABLE 16 Intermediate Structure & IUPAC name used ¹H NMR & LCMS data

  Compound-74 (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2- (2-aminoquinolin-7-yl)ethyl)bicyclo[3.1.0]hexane-2,3- diol 7-(2-((3aR,3bR,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2- dimethyl-hexahydrocyclopropa [3,4] cyclopenta[1,2-d][1,3]dioxol-3b-yl)ethyl)quinolin-2-amine ¹H NMR (400 MHz, DMSO-d6) δ 8.07 (s, 1H),7.82 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.2 Hz, 1H), 7.30 (d, J = 1.6 Hz,1H), 7.08-7.02 (m, 2H), 6.97 (s, 2H), 6.68 (d, J = 8.8 Hz, 1H), 6.58 (d,J = 3.5 Hz, 1H), 6.34 (s, 2H), 5.11 (d, J = 4.5 Hz, 1H), 4.91 (d, J =1.2 Hz, 1H), 4.55-4.49 (m, 2H), 3.73 (t, J = 5.2 Hz, 1H), 2.91-2.78 (m,2H), 2.10 (ddd, J = 13.6, 11.3, 5.3 Hz, 1H), 1.92- 1.85 (m, 1H),1.28-1.24 (m, 2H), 0.59 (td, J = 6.6, 3.2 Hz, 1H); LCMS m/z = 418.17(M + 2; 40%).

  Compound-75 (1R,2R,3S,4R,5S)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2- (2-aminoquinazolin-7-yl)ethyl)bicyclo[3.1.0]hexane-2,3- diol. N-(7-(2-((1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,3-dihydroxybicyclo[3.1.0]hexan- 1-yl)ethyl)quinazolin-2-yl)-2,2,2-trifluoroacetamide. ¹H NMR (400 MHz, DMSO-d6) δ 9.04 (s, 1H), 8.16(s, 1H), 7.71 (d, J = 8.2 Hz, 1H), 7.53 (s, 2H), 7.28 (s, 1H), 7.15 (dd,J = 11.1, 5.8 Hz, 2H), 6.83 (s, 2H), 6.69 (d, J =3.6 Hz, 1H), 5.14 (s,1H), 4.90 (s, 1H), 4.55 (s, 2H), 3.75 (s, 1H), 2.99-2.79 (m, 2H), 2.11(d, J = 15.9 Hz, 1H), 1.87 (q, J = 10.9, 8.1 Hz, 1H), 1.29-1.23 (m, 2H),0.61-0.56 (m, 1H); LCMS m/z = 418.10 (M + 1; 80%).

  Compound-76a and 76b (1S,2R,3S,4R,5S)-1-((S)-1-(2-Amino-3-bromoquinolin-7- yl)propan-2-yl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7- yl)bicyclo[3.1.0]hexane-2,3-diol.7-(2-((3aR,3bS,4aS,5R,5aS)- 5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3] dioxol-3b(3aH)-yl)propyl)-3-bromo-N-(4- methoxybenzyl) quinolin-2- amine.Diastereomeric mixture was separated by chiral preparative HPLC.Wavelength: 225 nm, Instrument Method: HEX-0.1% DEA_IPA-DCM_A_C_40_60_1.2ML 10MIN Flow Rate: 1.2 ml/min, Column: CHIRALPAK IACRL-025 Column Temp: 25° C., Mobile Phase A: HEX_0.1%DEA Mobile Phase C:IPA-DCM_1-1, Mobile Phase B: NA Mobile Phase D: NA First Diastereomer(Compound 76a): ¹H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 8.06 (s, 1H),7.58 (d, J = 8.2 Hz, 1H), 7.33 (s, 1H), 7.12 (d, J = 8.4 Hz, 1H),7.01-6.87 (m, 3H), 6.64- 6.47 (m, 3H), 5.13 (d, J = 5.2 Hz, 1H), 4.80(d, J = 2.9 Hz, 1H), 4.61 (t, J = 6.7 Hz, 1H), 4.47 (d, J = 7.2 Hz, 1H),3.96-3.85 (m, 1H), 3.22 (dd, J = 13.2, 3.9 Hz, 1H), 2.94-2.88 (m, 1H),1.97 - 1.83 (m, 1H), 1.31-1.21 (m, 2H), 0.79 (d, J = 6.8 Hz, 3H), 0.67-0.59 (m, 1H); LCMSm/z = 510.94 (M + 2; 40%) Second Diastereomer(Compound 76b): ¹H NMR (400 MHz, DMSO- d6) δ 8.32 (s, 1H), 8.06 (s, 1H),7.57 (d, J = 8.2 Hz, 1H), 7.32 (s, 1H), 7.11 (dd, J = 8.2, 1.6 Hz, 1H),7.07 (d, J = 3.6 Hz, 1H), 6.97 (s, 2H), 6.58 (d, J = 3.5 Hz, 1H), 6.55(s, 2H), 5.15 (d, J = 5.1 Hz, 1H), 4.80 (d, J = 2.6 Hz,1H), 4.64 (t, J =7.0 Hz, 1H), 4.43 (d, J = 7.3 Hz, 1H), 3.97-3.88 (m, 1H), 3.07-2.97 (m,1H), 2.97-2.88 (m, 1H), 1.70-1.55(m, 1H), 1.31-1.21 (m, 2H), 0.98 (d, J= 6.8 Hz, 3H), 0.61-0.52 (m, 1H); LCMS m/z = 510.94 (M + 2; 40%)

  Compound-77a and 77b (1S,2R,3S,4R,5S)-1-((S)-2-(2-Amino-3-chloro-5-fluoroquinolin- 7-yl)-1-cyclopropylethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin- 7-yl)bicyclo[3.1.0]hexane-2,3-diol.7-(2-((3aR,3bS,4aS,5R,5aS)- 5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2- dimethyltetrahydrocyclo-propa[3,4]cyclopenta[1,2- d][1,3] dioxol-3b(3aH)-yl)-2- cyclopropylethyl)-3-chloro-5- fluoro-N-(4- methoxybenzyl)quinolin-2- amine.Diastereomeric mixture was separated by chiral preparative HPLC.Wavelength: 225 nm, Instrument Method: MeOH_0.1%DEA_ 100_1.0ML_12MINFlow Rate: 1.00 ml/min Column: CHIRALPAK IE CRL-042 Column Temp: 30° C.,Mobile Phase A: MEOH_0.1%DEA, Mobile Phase B: NA First Diastereomer(Compound 77a): ¹H NMR (400 MHz, DMSO-d6) δ 8.39 (s, 1H), 8.16 (s, 1H),8.04 (s, 1H), 7.28 (s, 1H), 7.05 (dd, J = 11.3, 1.3 Hz, 1H), 6.93 (dd, J= 11.6, 8.0 Hz, 4H), 6.52 (d, J = 3.5 Hz, 1H), 5.28-5.08 (m, 1H), 4.82(d, J = 2.8 Hz, 1H), 4.61 (d, J = 6.7 Hz, 1H), 3.86 (s, 1H), 2.90 (dd, J= 13.3, 8.5 Hz, 1H), 2.77 (q, J = 7.2 Hz, 2H), 2.68 (q, J = 1.8 Hz, 1H),1.37 (dd, J = 8.8, 4.0 Hz,1H), 1.27- 1.01 (m, 3H), 0.66 (dd, J = 8.6,4.9 Hz, 1H), 0.46 (s, 1H), 0.26-0.17 (m, 1H), 0.16-0.01 (m, 1H), LCMSm/z = 509.4 (M + 1; 50%) Second Diastereomer (Compound 77b): ¹H NMR (400MHz, DMSO- d6) δ 8.15 (s, 1H), 8.05 (s, 1H), 7.31- 7.17 (m, 2H),7.08-6.81 (m, 5H), 6.59 (d, J = 3.5 Hz, 1H), 5.18 (s, 1H), 4.82 (dd, J =9.3, 4.6 Hz, 2H), 4.54 (s, 1H), 3.92(d, J = 6.7 Hz, 1H), 3.16 (q, J =6.5 Hz, 1H), 2.99-2.89 (m, 1H), 1.22-1.06 (m, 4H), 0.57 (q, J = 8.5, 7.9Hz, 1H), 0.50-0.34 (m, 1H), 0.26 (ddd, J = 13.1, 8.4, 4.7 Hz, 2H), 0.06(dd, J = 9.4, 4.7 Hz, 1H) ; LCMS m/z = 509.4 (M + 1; 50%)

  Compound-78a and 78b (1S,2R,35,4R,5S)-1-(1-(2-Amino-3-chloro-5-fluoroquinolin-7- yl)propan-2-yl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7- yl)bicyclo[3.1.0]hexane-2,3-diol.N-(7-(2-((1S,2R,3S,4R,5S)-4- (4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,3- dihydroxybicyclo [3.1.0]hexan-1-yl)propyl)-3-chloro- 5-fluoroquinolin-2-y1)-2,2,2-trifluoroacetamide. First Diastereomer(Compound-78a): ¹H NMR (400 MHz,DMSO-d6) δ 8.15 (s, 2H), 8.06 (s, 1H), 7.17 (s, 1H), 7.07 (d, J = 3.6Hz, 1H), 7.04-6.90 (m, 4H), 6.58 (d, J = 3.5 Hz, 1H), 5.16 (d, J = 5.1Hz, 1H), 4.79 (d, J = 2.6 Hz, 1H), 4.63 (t, J = 7.1 Hz, 1H), 4.45 (d, J= 7.3 Hz, 1H), 3.93 (d, J = 6.9 Hz, 1H), 2.99 (dd, J = 13.3, 4.9 Hz,1H), 2.61 (d, J = 11.2 Hz, 1H), 1.63 (s, 1H), 1.17 (d, J = 5.8 Hz, 2H),0.99 (d, J = 6.7 Hz, 3H), 0.57 (d, J = 4.3 Hz, 1H); LCMS m/z = 485.03(M + 2; 40%) Second Diastereomer (Compound- 78b): ¹H NMR (400 MHz, DMSO-d6) δ 8.16 (s, 1H), 8.08 (s, 1H), 7.19 (s, 1H), 7.10 (s, 2H), 6.98 (dd,J = 10.0, 2.2 Hz, 2H), 6.92 (s, 2H), 6.56 (d, J = 3.6 Hz, 1H), 5.13 (d,J = 5.3 Hz, 1H), 4.80 (d, J = 2.9 Hz, 1H), 4.61 (t, J = 6.7 Hz, 1H),4.48 (d, J = 7.1 Hz, 1H), 3.90 (s, 1H), 3.21 (dd, J = 13.3, 4.1 Hz, 1H),2.68 (p, J = 1.9 Hz, 1H), 2.36-2.32 (m, 1H), 1.17 (t, J = 4.3 Hz, 2H),0.79 (d, J = 6.8 Hz, 3H), 0.63 (dd, J = 8.6, 4.7 Hz, 1H); LCMS m/z =483.02 (M+; 90%)

  Compound-79a and 79b (1R,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(2- (2-aminoquinolin-7-yl)propyl)bicyclo[3.1.0]hexane-2,3-diol. 7-(1-((3aR,3bR,4a5,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)-2,2-dimethyltetrahydrocyclo- prop[3,4]cyclopenta[1,2- d[1,3]dioxol-3b-(3aH)- yl)propan-2-yl)-N-(4- methoxybenzyl)quinolin-2- amine.Diastereomeric mixture was separated by chiral preparative HPLC.Wavelength: 225 nm, Instrument Method: MeOH_0.1%DEA_A_1.0ML_10MIN FlowRate: 1.00 ml/min, Column: CHIRALPAK IB CRL-043 Column Temp: 30° C.,Mobile Phase A: MeOH_0.1%DEA,Mobile Phase B: NA FirstDiastereomer(Compound 79a): ¹H NMR (400 MHz, DMSO-d6) δ 8.13-8.03 (m,2H), 7.66 (d, J = 8.2 Hz, 1H), 7.53-7.43 (m, 3H) 7.31 (d, J = 8.3 Hz,1H), 7.03 (s, 2H), 6.93 (d, J = 3.5 Hz, 1H), 6.84 (d, J = 9.1 Hz, 1H),6.56 (d, J = 3.5 Hz, 1H), 5.15 (d, J = 4.7 Hz, 1H), 4.76 (d, J = 1.4 Hz,1H), 4.49-4.32 (m, 2H), 3.70 (t, J = 5.5 Hz, 1H), 3.30-3.18 (m, 1H),2.25(dd, J = 14.1, 4.8 Hz, 1H), 1.82 (dd, J = 14.2, 9.1 Hz, 1H), 1.31-1.22(m, 4H), 1.02- 0.91 (m, 1H), 0.64 (dd, J = 8.5, 4.7 Hz, 1H); LCMS m/z =430.92 (M + 1; 90%). Second Diastereomer(Compound 79a): ¹H NMR (400 MHz,DMSO-d6) δ 8.02 (d, J = 13.7 Hz, 2H), 7.64 (d, J = 8.2 Hz, 1H), 7.37 (d,J = 1.6 Hz, 1H), 7.21 (dd, J = 8.2, 1.6 Hz, 3H), 6.98 (s, 2H), 6.81 (d,J = 9.0 Hz, 1H), 6.69 (d, J = 3.6 Hz, 1H), 6.42 (d, J = 3.5 Hz, 1H),5.16 (d, J = 4.8 Hz, 1H), 4.83 (d, J = 1.7 Hz, 1H), 4.47 (d, J = 2.4 Hz,2H), 3.68 (s, 1H), 2.37-2.27 (m, 1H), 1.68-1.57 (m, 1H), 1.39-1.26 (m,5H), 1.04 (dd, J = 8.6, 3.8 Hz, 1H), 0.69-0.60 (m, 1H); LCMS m/z =430.98 (M + 1; 90%)

  Compound-80 (1R,2R,3S,4R,5S)-1-(((2-Amino-3-bromoquinolin-7-yl)oxy)methyl)-4- (4-amino-7H-pyrrolo[2,3-d]pyrimidin-7- y1)bicyclo[3.1.0]hexane-2,3-diol.N-(7-(((1R,2R,3S,4R,5S)-4- (4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,3- dihydroxybicyclo[3.1.0]hexan- 1-yl)methoxy)-3-bromoquinolin-2-yl)-2,2,2- trifluoroacetamide. ¹H NMR (400 MHz, DMSO-d6)δ 9.39 (bs, 2H), 8.45-8.36 (m, 3H), 7.83-7.62 (m, 2H), 7.03-7.14 (m,3H), 6.99 (d, J = 3.6 Hz, 1H), 5.28 (s, 1H), 5.05 (s, 1H), 4.86 (s, 1H),4.71- 4.57 (m, 2H),3.93 (d, J = 10.4 Hz, 1H), 3.72 (d, J = 6.4 Hz, 1H),1.62 (d, J = 8.6 Hz, 1H), 1.53 (t, J = 4.4 Hz, 1H), 0.90-0.82 (m, 1H);LCMS m/z = 499.2 (M + 2; 40%).

  Compound-81 (1S,2R,3S,4R,5S)-4-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1- (((2-aminoquinolin-7- yl)thio)methyl)bicyclo [3.1.0] hexane-2,3-diol. 7-((((3aR,3bS,4aS,5R,5aS)-5-(4-Amino-7H-pyrrolo[2,3- d]pyrimidin-7-y1)-2,2- dimethyltetrahydrocyclo- propa [3,4]cyclopent[1,2- d][1,3]dioxol-3b(3aH)-yl)methyl)thio)-N-(4- methoxybenzyl)quinolin-2- amine. ¹H NMR (400 MHz,DMSO-d6) δ 8.05 (s, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 8.4 Hz,1H), 7.38(d, J = 1.8 Hz, 1H), 7.16 (d, J = 3.5 Hz, 1H), 7.13 (dd, J =8.4, 1.9 Hz, 1H), 6.96 (s, 2H), 6.67 (d, J = 8.8 Hz, 1H), 6.52 (d, J =3.5 Hz, 1H), 6.44 (s, 2H), 5.21-5.11 (m, 1H), 4.90 (s, 1H), 4.68 (d, J =7.1 Hz, 1H), 4.57 (s, 1H), 3.71-3.60 (m, 2H), 3.38 (d, J = 13.5 Hz, 1H),1.43- 1.38 (m, 2H), 0.84-0.77 (m, 1H); LCMS m/z = 435.10 (M + 2; 90%).

Example-7:(1R,2R,3S,4R,5S)-1-(2-(?2-Amino-3-(4-fluorophenyl)quinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(Compound-82)

In a sealed tube, the mixture of(1R,2R,3S,4R,5S)-1-(2-(2-amino-3-bromoquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol(100 mg, 0.202 mmol), K₂CO₃ (84 mg, 0.606 mmol), (4-fluorophenyl)boronicacid (42.4 mg, 0.303 mmol) in dioxane (10 ml) was deggassed for 10 minwith nitrogen at 25° C. PdCl₂(dppf)-CH₂Cl₂ adduct (16.49 mg, 0.020 mmol)was added and stirred the reaction mixture at 100° C. for 16 h. Theresulting mixture was filtered through cellite and filtrate wasconcentrated in vacuo to get 0.15 g of crude compound. This residue waspurified by combiflash (R_(f)200, Teledyne/Isco) instrument onto aRedisep® R_(f) column with gradient elution (0 to 8%) of methanol indichloromethane to afford the title compound (0.025 g, 93.81%) as anoff-white solid. ¹H NMR (400 MHz, DMSO-d₆) δ 8.07 (s, 1H), 7.78 (s, 1H),7.68-7.50 (m, 3H), 7.43-7.24 (m, 3H), 7.13 (dd, J=8.2, 1.7 Hz, 1H), 7.05(d, J=3.6 Hz, 1H), 6.97 (s, 2H), 6.59 (d, J=3.5 Hz, 1H), 5.96 (s, 2H),5.11 (d, J=4.5 Hz, 1H), 4.97-4.81 (m, 1H), 4.58-4.39 (m, 2H), 3.74 (t,J=5.5 Hz, 1H), 3.04-2.72 (m, 2H), 2.18-2.09 (m, 1H), 1.90 (td, J=12.5,5.6 Hz, 1H), 1.34-1.16 (m, 2H), 0.64-0.54 (m, 1H); LCMS m/z=511.09 (M+1;90%).

Examples in table-17 were synthesized by following an analogous reactionprotocol as was used for the preparation of(1R,2R,3S,4R,5S)-1-(2-(2-amino-3-bromoquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol using theappropriate starting materials.

TABLE 17 Structure & IUPAC name Intermediate used ¹H NMR & LCMS data

  Compound-83 (1R,2R,3S,4R,5S)-1-(2-(2- Amino-3-(pyridin-3-yl)quinolin-7-yl)ethyl)-4-(4-amino-7H- pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol. (1R,2R,3S,4R,5S)-1-(2- (2-Amino-3-bromoquinolin-7- yl)ethyl)-4-(4-amino-7H- pyrrolo[2,3-d]pyrimidin-7yl)bicyc1o[3.1.0]hexane- 2,3-diol. ¹H NMR (400 MHz, DMSO-d₆) δ 8.07 (s,1H), 7.78 (s, 1H), 7.68- 7.50 (m, 3H), 7.43-7.24 (m, 3H), 7.13 (dd, J =8.2, 1.7 Hz, 1H), 7.05 (d, J = 3.6 Hz, 1H), 6.97 (s, 2H), 6.59 (d, J =3.5 Hz, 1H), 5.96 (s, 2H), 5.11 (d, J = 4.5 Hz, 1H), 4.97-4.81 (m, 1H),4.58-4.39 (m, 2H), 3.74 (t, J = 5.5 Hz, 1H), 3.04-2.72 (m, 2H),2.18-2.09 (m, 1H), 1.90 (td, J = 12.5, 5.6 Hz, 1H), 1.34-1.16 (m, 2H),0.64-0.54 (m, 1H); LCMS m/z = 494.2(M + 1; 30%)

  Compound-84 (1R,2R,3S,4R,5S)-1-(2-(2- Amino-3-(3-methyl isoxazol-4-yl)quinolin-7-yl)ethyl)-4-(4- amino-7H-pyrrolo[2,3- d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol. (1R,2R,3S,4R,5S)-1-(2- (2-Amino-3-bromoquinolin-7- yl)ethyl)-4-(4-amino-7H- pyrrolo[2,3-d]pyrimidin- 7-yl)bicyclo[3.1.0]hexane- 2,3-diol ¹H NMR (400 MHz, DMSO-d6) δ 9.01 (s,1H), 8.07 (s, 1H), 7.85 (s, 1H), 7.59 (d, J = 8.2 Hz, 1H), 7.37 (d, J =1.5 Hz, 1H), 7.13 (dd, J =8.2, 1.6 Hz, 1H), 7.04 (d, J = 3.6 Hz, 1H),6.97 (s, 2H), 6.58 (d, J =3.5 Hz, 1H), 6.15 (s, 2H), 5.12 (d, J = 4.1Hz, 1H), 4.59-4.47 (m, 2H), 3.74 (d, J = 5.2 Hz, 1H), 3.00-2.77 (m, 3H),2.22 (s, 3H), 1.89 (ddd, J = 13.9, 11.4, 5.7 Hz, 1H), 1.30-1.25 (m, 2H),0.90-0.80 (m, 1H), 0.59 (q, J = 5.8 Hz, 1H); 498.07 (M + 1; 100%)

BIOLOGICAL EXAMPLES Biochemical Assay Protocol 1

Inhibitory effect of compounds on PRMT5 was assessed using HTRFdetection technology in biochemical assay. Biotinylated H4R3 (residues1-21) was used as a substrate. Compounds were pre-incubated with 15-25ng PRMT5:MEP50 per well of a 384-well plate for 30 min at roomtemperature in the assay buffer containing 20 mM Bicine, pH 7.6, 25 mMNaCl, 2 mM DTT, 0.01% Chicken albumin and 0.01% Tween-20. Reaction wasinitiated by adding 1 μM of SAM and 50 nM biotinylated H4R3. Total assayvolume was 15 μL. Reaction was continued for 120 min at roomtemperature. Then detection solution containing Streptavidin-Eucryptate, anti-rabbit IgG-XL-665, Histone H4R3 Dimethyl Symmetric(H4R3me2s) Polyclonal Antibody, all prepared in HTRF detection bufferwas added and further incubated for 30 min at room temperature. HTRFsignal was recorded in PHERAStar microplate reader. Ratio of signalobtained at 665 nm and 620 nm was used to compute the percent inhibitionof compound as follows

% Inhibition=100−((Test Ratio−Negative control Ratio)/(Positive controlRatio−Negative control Ratio)*100) where

Positive control=PRMT5+SAM+H4R3

Negative control=PRMT5+H4R3

Biochemical Assay Protocol 2

Inhibitory effect of compounds on PRMT5 was assessed using HTRFdetection technology in biochemical assay. Biotinylated H4R3 (residues1-21) was used as a substrate. Compounds were pre-incubated with 2.5 ngPRMT5:MEP50 per well of a 384-well plate for 30 min at room temperaturein the assay buffer containing 20 mM Bicine, pH 7.6, 25 mM NaCl, 2 mMDTT, 0.01% Chicken albumin and 0.01% Tween-20. Reaction was initiated byadding 1 μM of SAM and 50 nM biotinylated H4R3. Total assay volume was15 μL. Reaction was continued for 4 h at room temperature. Thendetection solution containing Streptavidin-Eu cryptate, anti-rabbitIgG-XL-665, Histone H4R3 Dimethyl Symmetric (H4R3me2s) PolyclonalAntibody, all prepared in HTRF detection buffer was added and furtherincubated for 30 min at room temperature. HTRF signal was recorded inPHERAStar microplate reader. Ratio of signal obtained at 665 nm and 620nm was used to compute the percent inhibition of compound as follows

% Inhibition=100−((Test Ratio−Negative control Ratio)/(Positive controlRatio−Negative control Ratio)*100) where

Positive control=PRMT5+SAM+H4R3

Negative control=PRMT5+H4R3

Activity Range Compound numbers IC₅₀ 300 pM to 43, 26, 35b, 47, 21, 38,34b, 34a, 7a, 13, 37, 18, 33b, 950 pM 33a, 76a, 23, 25, 24, 48, 1, 61,73, 44, 2, 15, 36a, 45a, 45b, 35a

SDMA Inhibition Assay Protocol

Z-138 cells (ATCC, CRL-3001′) were seeded at a density of 1 millioncells/well in transparent, flat bottomed tissue culture grade 48-wellplates. Cells were treated with various concentration of test compoundsfor a period of 48 h. Cell lysate was prepared using 1×CST Lysis buffer(Cell Signaling Technology, USA) and 500 ng/well/50 μL of lysate in pH9.6 carbonate buffer was coated on 96-well Maxisorb plate and incubatedovernight at 4° C. The plate was washed twice in 1×PBS containing 0.05%Tween 20 and blocked in 1% BSA for 1 h at ambient temperature. Further,the plate was incubated first with primary antibody (anti-SDMA antibody;CST #13222s) at ambient temperature for 2 h and then with HRP-conjugatedsecondary antibody at ambient temperature for 1 h with 2 intermittentwashing steps in between.

For luminiscence based detection, HRP substrates (substrate A+substrateB in a 1:1 proportion) were added followed by luminiscence reading after30 min in Synergy™ 2 reader (Biotek, USA).

For absorbance based detection, TMB substrate was added followed byaddition of STOP solution (2N H₂SO₄) post colour development andabsorbance (excitation 450 nm and emission 540 nm) was measured inSynergy™ 2 reader (Biotek, USA). % inhibition of SDMA was calculatedrelative to the vehicle control samples containing media with 0.1% DMSOalone as per the formula below.

(Avg. of Untreated Control−Avg. of Test)×100

Avg. of Untreated Control

The IC₅₀ values of individual compounds were calculated with Non LinearRegression Analysis using Graph Pad Prism (Graph Pad software, Inc,USA).

Activity Range Compound numbers IC₅₀ 1 pM to 7b, 13, 37, 33b, 46, 76b,23, 24, 2, 48, 1, 61, 73, 47, 38, 1 nM 34b, 30, 41, 31, 72, 29, 34a, 21,35a, 26, 43. IC₅₀ 1.1 nM to 32, 64, 33a, 76a, 25, 62, 35b. 50 nM

Anticancer Activity Assay

Z-138 cells were seeded at a density of 2000-3000 cells per well inculture media (IMDM+10% FBS). PANC-1 (ATCC, CRL-1469™) and MIA PaCa-2(ATCC, CRL-1420™) cells were seeded at a density of 200-300 cells perwell in culture media (DMEM+10% FBS). Cells were seeded in opaque, flatbottomed tissue culture grade 96-well plates and Z-138 cells(suspension) were seeded and treated on the same day with variousconcentrations of test compounds. PANC-1 and MIA PaCa-2 cells, beingadherent, were kept for overnight settlement at standard cell cultureconditions (37° C., 5% CO₂). On the following day, cells were treatedwith various concentrations of test compounds. Cells were treated withtest compounds for a period of 96 h, 7 days and 10 days, for Z-138cells, PANC-1 cells and MIA PaCa-2 cells, respectively. Cell viabilitywas assessed using CellTiterGlo™ (Promega, USA) as per manufacturer'sinstructions. Relative Light Units (RLU) were read in Synergy™ 2 reader(Biotek, USA). The assay measures cellular ATP as an indicator of cellviability. RLU is proportional to the number of viable cells in therespective well.

% inhibition of cell viability was calculated relative to the vehiclecontrol samples containing media with 0.1% DMSO alone as per the formulabelow.

(Avg. of Untreated Control−Avg. of Test)×100

Avg. of Untreated Control

The IC₅₀ values of individual compounds were calculated with Non LinearRegression Analysis using Graph Pad Prism (Graph Pad software, Inc,USA).

Anti-Cancer Assay (Z-138)

Activity Range Compound numbers IC₅₀ 0.1 pM to 43, 35a, 47, 21, 40, 38,34a, 13, 37, 18, 33b, 46, 76b, 100 pM 24, 2, 48, 1, 54, 61, 73, 34b, 7a,25, 33a, 44, 72. IC₅₀ 101 pM to 26, 64, 39, 7b, 76a, 62, 20b 1 nM

Anti-Cancer Assay (Panc-1)

Activity Range Compound numbers IC₅₀ 300 pM to 41, 47, 64, 40, 21, 38,34b, 34a, 7b, 13, 37, 33b, 46, 20 nM 25, 24, 48, 61, 73, 18, 30, 7a, 2,1, 54, 35a, 43 IC₅₀ 20 nM to 39, 29, 33a, 76b, 62 100 nM

Anti-Cancer Assay (MiaPaCa-2)

Activity Range Compound numbers IC₅₀ 1 pM to 21, 38, 34b, 34a, 13, 37,33b, 25, 24, 2, 48, 1, 61, 73, 40 nM 18, 30, 40, 64, 62, 33a, 35a, 43,26

In Vivo Efficacy Experiments

Tumor xenograft for mantle cell lymphoma was established by injection ofcells into the right flank of female NOD.CB17-Prkdc<scid>/J mice with anage between 7-11 weeks purchased from The Jackson Laboratory, USA. Allanimal study proposals were reviewed and approved by the InstitutionalAnimal Ethics Committee (IAEC) prior to initiation of experimentation.

Z-138 Xenograft

For Z-138 xenograft mouse model, Z-138 cells (ATCC® CRL-3001™) weregrown in IMDM medium supplemented with 10% FBS. Cells were incubatedunder standard conditions at 37° C. and 5% CO₂. For generating tumors,Z-138 cells in IMDM medium were mixed with Matrigel (Corning® Matrigel®Basement Membrane Matrix) in a ratio of 1:1. 10×10⁶ cells) in a volumeof 200 μL were injected subcutaneously in each mouse to establishtumors. Mice were randomized into treatment groups of 8-10 mice, oncetumors reached an average volume between 100 to 120 mm³. Treatment wasinitiated on day of randomization and continued until end of the study.The Vehicle and test compound treatment groups were administeredrespective treatments orally, using gavage tubing, at an applicationvolume of 10 mL/kg per mouse twice a day.Mice were housed in individually ventilated cages (IVC) at roomtemperature of 22+3° C., humidity 50+20% and 12/12 h light/dark cycle.All the experimental activities were carried-out inside the biosafetycabinets to ensure sterility.

Tumor size was measured with Digimatic Vernier caliper (Mitutoyo, Japan)when the tumors became palpable. Tumor volume (T. V.) is calculated byusing the formula:

Tumor volume (mm3)=(L×W2)/2

Where, L: Length of tumor, W: Width of tumor in millimeterPercent tumor growth inhibition (% TGI) is calculated using the formula:

% TGI=[1−(Tf−Ti)/(Cf−Ci)]×100

Where, Tf and Ti, are the final and initial tumor volumes (testcompound), and Cf and Ci are the final and initial mean tumor volumes(vehicle group), respectively.Percent tumor regression is calculated as:

% TR: (Ti−Tf)/(Ti)×100

Where, Tf and Ti, are the final and initial tumor volumes, respectively.The compounds 24, 33b, and 13 were tested for tumor growth inhibition inZ-138 xenograft model using assay procedure given above; the % of tumorgrowth inhibition after 38 days at 1 mg/kg dose was found to be 100% andtumor regression was 67-74%. The compound-48 was tested at 5 mg/kg dose,it showed 100% tumor growth inhibition and 63% tumor regression.

1. A compound having the general formula (I), a stereoisomer thereof, ora pharmaceutically acceptable salt thereof,

wherein, L₁ is selected from —CR^(a)R^(b)—, —NR^(a)—, S, and O; Z isselected from CH and N; R^(a) and R^(b) are independently selected ateach occurrence from hydrogen, substituted or unsubstituted alkyl, andsubstituted or unsubstituted cycloalkyl; ring A is selected from,

R^(c) and R^(d) are selected from substituted or unsubstituted alkyl ortogether with the carbon atoms to which they are attached form a C₃-C₆cycloalkyl ring; R is selected from —NR⁴R⁵, hydrogen, halogen,substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy,substituted or unsubstituted heteroaryl and substituted or unsubstitutedcycloalkyl; R¹ and R² together with the carbon atoms to which they areattached form a bond in order to form a —C═C—; or R¹ and R² togetherwith the carbon atoms to which they are attached form a cyclopropanering; R^(2′) and R^(2a) which may be same or different and areindependently selected from hydrogen and substituted or unsubstitutedalkyl; R³ is independently selected at each occurrence from halogen,cyano, nitro, substituted or unsubstituted alkyl, —OR⁶, —NR⁷R⁸,substituted or unsubstituted cycloalkyl, —C(O)OH, —C(O)O-alkyl, —C(O)R⁹,—C(O)NR⁷R⁸, —NR⁷C(O)R⁹, substituted or unsubstituted aryl, substitutedor unsubstituted heteroaryl, and substituted or unsubstitutedheterocyclyl; R⁴ and R⁵ are independently selected from hydrogen,substituted or unsubstituted alkyl, and substituted or unsubstitutedcycloalkyl; R⁶ is selected from hydrogen, substituted or unsubstitutedalkyl, and substituted or unsubstituted cycloalkyl; R⁷ and R⁸ areindependently selected from hydrogen, substituted or unsubstitutedalkyl, and substituted or unsubstituted cycloalkyl; R⁹ is selected fromsubstituted or unsubstituted alkyl and substituted or unsubstitutedcycloalkyl; R¹⁰ is selected from hydrogen, halogen, and substituted orunsubstituted alkyl; ‘n’ is an integer ranging from 0 to 4, bothinclusive; when an alkyl group is substituted, it is substituted with 1to 4 substituents independently selected from oxo (═O), halogen, cyano,cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR^(7a), —C(═O)OH,—C(═O)O(alkyl), —NR^(8a)R^(8b), —NR^(8a)C(═O)R^(9a), and—C(═O)NR^(8a)R^(8b); when the heteroaryl group is substituted, it issubstituted with 1 to 4 substituents independently selected fromhalogen, nitro, cyano, alkyl, haloalkyl, perhaloalkyl, cycloalkyl,heterocyclyl, aryl, heteroaryl, —OR^(7a), —NR^(8a)R^(8b),—NR^(7a)C(═O)R^(9a), —C(═O)R^(9a), —C(═O)NR^(8a)R^(8b), —SO₂-alkyl,—C(═O)OH, and —C(═O)O-alkyl; when the heterocycle group is substituted,it is substituted either on a ring carbon atom or on a ring hetero atom,and when it is substituted on a ring carbon atom, it is substituted with1 to 4 substituents independently selected from oxo (═O), halogen,cyano, alkyl, cycloalkyl, perhaloalkyl, —OR^(7a), —C(═O)NR^(8a)R^(8b),—C(═O)OH, —C(═O)O-alkyl, —N(H)C(═O)(alkyl), —N(H)R^(8a), and —N(alkyl)₂;and when the heterocycle group is substituted on a ring nitrogen, it issubstituted with substituents independently selected from alkyl,cycloalkyl, aryl, heteroaryl, —SO₂(alkyl), —C(═O)R^(9a), and—C(═O)O(alkyl); when the heterocycle group is substituted on a ringsulfur, it is substituted with 1 or 2 oxo (═O) group(s); R^(7a) isselected from hydrogen, alkyl, perhaloalkyl, and cycloalkyl; R^(8a) andR^(8b) are each independently selected from hydrogen, alkyl, andcycloalkyl; and R^(9a) is selected from alkyl and cycloalkyl.
 2. Thecompound of claim 1 having the structure of Formula (II), a stereoisomerthereof, or a pharmaceutically acceptable salt thereof,

wherein, Ring A, Z, L₁, R^(a), R^(b), R^(2′), R, R^(2a), R³, R¹⁰ and ‘n’are as defined herein above.
 3. The compound of claim 1 having thestructure of Formula (III), a stereoisomer thereof, or apharmaceutically acceptable salt thereof,

wherein, Ring A, Z, L₁, R^(a), R^(b), R^(2′), R, R^(2a), R³, R¹⁰ and ‘n’are as defined herein above.
 4. The compound of claim 1 having thestructure of Formula (IV), a stereoisomer thereof, or a pharmaceuticallyacceptable salt thereof,

wherein, X² is Br or Cl; L₁, R^(a), R^(b), R¹, R^(2′), R², R, R^(2a) andR¹⁰ are as defined herein above.
 5. The compound of claim 1, whereinring A is selected from—


6. The compound of claim 1, wherein L₁ is selected from —CH₂—,—CH(CH₃)—, —NH—, —N(CH₃)—, S, and O.
 7. The compound of claim 1, whereinR³ is selected from F, Cl, Br, CN, —NH₂, —NH(CH₃), —NHCH(CH₃)₂, —CH₃,cyclopropyl, —CH(CH₃)₂, —CF₂CH₃, —OCH₃, CF₃,


8. The compound of claim 1, wherein R is selected from hydrogen, —NH₂,Cl, —CH(CH₃)₂, methyl, ethyl, cyclopropyl and


9. The compound of claim 1, wherein R^(a) and R^(b) are independentlyselected from hydrogen, methyl, and cyclopropyl.
 10. The compound ofclaim 1, wherein R^(2′) and R^(2a) are independently selected fromhydrogen and methyl.
 11. The compound of claim 1, wherein R¹⁰ isselected from hydrogen, —F, and methyl.
 12. The compound of claim 1,wherein ring A is selected from—

L1 is selected from —CH2-, —CH(CH3)-, —NH—, —N(CH3)-, S, and O; R³ isselected from F, Cl, Br, CN, —NH₂, —NH(CH₃), —NHCH(CH₃)₂, —CH₃,cyclopropyl, —CH(CH₃)₂, —CF₂CH₃, —OCH₃, CF₃,

R is selected from hydrogen, —NH₂, Cl, —CH(CH₃)₂, methyl, ethyl,cyclopropyl and

R^(a) and R^(b) are independently selected from hydrogen, methyl, andcyclopropyl; R^(2′) and R^(2a) are independently selected from hydrogenand methyl; R¹⁰ is selected from hydrogen, —F, and methyl.
 13. Thecompound having the general formula (I), a stereoisomer thereof, or apharmaceutically acceptable salt thereof, as claimed in claim 1, whereinthe compound is selected from:(1S,2R,5R)-3-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(((2-amino-3-chloroquinolin-7-yl)thio)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-Amino-3-bromoquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol(Compound-9);(1S,2R,5R)-3-(1-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(2-(2-Amino-3-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-8-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3,5-dichloroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-amino-3-chloroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-ethylcyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-ethyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-cyclopropyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-1H-pyrrolo[3,2-c]pyridin-1-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-Amino-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-methylquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;(1R,2R,3S,4R,5S)-1-(2-(2-amino-3-bromo-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;and(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo [3.1.0]hexane-2,3-diol.
 14. The compoundhaving general formula (I), a stereoisomer thereof, or apharmaceutically acceptable salt thereof, as claimed in claim 1, whereinthe compound is selected from:(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo [3.1.0]hexane-2,3-diol;(1S,2R,5R)-3-(2-(2-Amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-amino-3-chloro-6-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(((2-amino-3-chloro-5-fluoroquinolin-7-yl)oxy)methyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-amino-3-chloroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-amino-3-chloro-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-methylcyclopent-3-ene-1,2-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-chloroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;(1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(1-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)propan-2-yl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1S,2R,5R)-3-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopent-3-ene-1,2-diol;(1R,2R,3S,4R,5S)-1-(2-(2-Amino-3-bromo-5-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol;and(1R,2R,3S,4R,5S)-1-(2-(2-amino-3-bromo-6-fluoroquinolin-7-yl)ethyl)-4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[3.1.0]hexane-2,3-diol.15. A pharmaceutical composition comprising at least one compound ofclaim 1, a stereoisomer thereof, or a pharmaceutically acceptable saltthereof, and a pharmaceutically acceptable carrier.
 16. A method fortreating the diseases, disorders, syndromes or conditions associated byinhibition of PRMT5 enzyme to a subject in need thereof, comprisingadministering to the subject, an effective amount of compound as claimedin claim 1, or their pharmaceutically acceptable salt thereof.
 17. Amethod as claimed in claim 16, wherein the said diseases, disorders,syndromes or conditions associated by inhibition of PRMT5 enzyme isglioblastoma multiforme, prostate cancer, pancreatic cancer, mantle celllymphoma, non-Hodgkin's lymphomas and diffuse large B-cell lymphoma,acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma,non-small cell lung cancer, small cell lung cancer, breast cancer,triple negative breast cancer, gastric cancer, colorectal cancer,ovarian cancer, bladder cancer, hepatocellular cancer, melanoma,sarcoma, oropharyngeal squamous cell carcinoma, chronic myelogenousleukemia, epidermal squamous cell carcinoma, nasopharyngeal carcinoma,neuroblastoma, endometrial carcinoma, and cervical cancer.
 18. A methodas claimed in claim 16, wherein the said diseases, disorders, syndromesor conditions associated by inhibition of PRMT5 enzyme is cancer. 19.Use of a compound, of claim 1, in the preparation of medicament fortreating the diseases, disorders, syndromes or conditions associated byinhibition of PRMT5 in a subject in need thereof.
 20. The use as claimedin claim 19, wherein the diseases, disorders, syndromes or conditionsassociated by inhibition of PRMT5 are selected from the group consistingof glioblastoma multiforme, prostate cancer, pancreatic cancer, mantlecell lymphoma, non-Hodgkin's lymphomas and diffuse large B-celllymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, multiplemyeloma, non-small cell lung cancer, small cell lung cancer, breastcancer, triple negative breast cancer, gastric cancer, colorectalcancer, ovarian cancer, bladder cancer, hepatocellular cancer, melanoma,sarcoma, oropharyngeal squamous cell carcinoma, chronic myelogenousleukemia, epidermal squamous cell carcinoma, nasopharyngeal carcinoma,neuroblastoma, endometrial carcinoma, and cervical cancer.
 21. The useas claimed in claim 19, wherein the diseases, disorders, syndromes orconditions associated by inhibition of PRMT5 is cancer.